Nanotechnology for Neurodegenerative Diseases: Recent Progress in Brain-Targeted Delivery, Stimuli-Responsive Platforms, and Organelle-Specific Therapeutics
Open accessAbstract
Neurodegenerative diseases-including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis-are characterized by progressive neuronal loss and complex pathological mechanisms such as protein aggregation, mitochondrial dysfunction, and neuroinflammation. Conventional therapies offer limited efficacy due to the blood-brain barrier (BBB) and lack of targeted delivery. Nanotechnology has emerged as a transformative strategy for precise brain-targeted treatment. This review summarizes recent advances in nanoparticle-based drug delivery systems, including polymeric nanoparticles, liposomes, inorganic nanomaterials, and biomimetic carriers, highlighting their design features, BBB-penetration mechanisms, and disease-specific applications. Emphasis is placed on stimuli-responsive nanocarriers that react to pH, reactive oxygen species, or enzyme activity, enabling site-specific drug release. Additionally, organelle-targeting strategies-particularly those directed at mitochondria and lysosomes-are explored for their role in subcellular precision therapy. The integration of diagnostic and therapeutic modalities in theranostic nanoplatforms is also discussed. By consolidating preclinical progress and emerging technologies, this review offers insights into the future of nanomedicine in treating neurodegenerative diseases and lays the groundwork for clinical translation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NPs can be designed specifically to be cleaved when in contact with enzymes such as esterases, proteases, and phosphatases, destroying a bond that allows the release of the therapeutic agent.
“For this reason, NPs can be designed specifically to be cleaved when in contact with these enzymes, destroying a bond that allows the release of the therapeutic agent.”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [87]
The “Enzyme-Responsive Nanocarriers” subsection (page not provided) says that enzymes cleave peptides or chemical bonds in nanocarriers, initiating carrier disassembly and drug release. It gives acetylcholinesterase and proteases as examples, but does not identify phosphatases as triggers for this mechanism. (LLM, conf=0.86)
Experimental — accuracy not yet measuredROS-responsive NPs remain stable under physiological conditions but rapidly disassemble in high-ROS environments, allowing selective drug release at oxidative stress sites.
“Like pH-responsive NPs, these systems remain stable under physiological conditions but rapidly disassemble in high-ROS environments, allowing selective drug release at oxidative stress sites”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [87]
Incorporating genetic material into NPs can protect nucleic acid molecules and transport them to desired locations, overcoming challenges of nucleic acid delivery.
“Therefore, incorporating genetic material into NPs presents an appealing approach to overcome these challenges, since they can protect nucleic acid molecules as well as transport them to the desired locations [87,100].”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [87]
The complexity of design and clinical translation of stimuli-responsive nanocarriers remain obstacles to overcome.
“Nevertheless, the complexity of their design and the clinical translation remain obstacles to overcome”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [87]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204 · cited 1× · see citing works
“57 The impermeability of the BBB presents a major limitation for most conventional drugs, severely restricting their therapeutic efficacy.”
Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?
Leng, F., & Edison, P. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-020-00435-y · Cited by 3,179 · cited 1× · see citing works
“…long-standing therapeutic challenges—particularly the limited efficacy of conventional treatments and the formidable barrier posed by the BBB. 14 53 Nanocarrier systems, endowed with excellent biocompatibility, engineering versatility, and superior BBB penetration capabilities, provide…”
Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.188 · Cited by 3,076 · see citing works
Oxidative Stress: A Key Modulator in Neurodegenerative Diseases
Singh, A., Kukreti, R., Saso, L., & Kukreti, S. (2019) · Molecules · doi:10.3390/molecules24081583 · Cited by 2,305 · cited 1× · see citing works
“133 Excess ROS induces lipid peroxidation, DNA damage, and protein modifications, activates inflammatory cascades, and triggers neuronal apoptosis—key drivers of disease progression.”
Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,294 · see citing works
Pathology of Neurodegenerative Diseases
Dugger, B. N., & Dickson, D. W. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028035 · Cited by 1,665 · see citing works
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616 · cited 1× · see citing works
“129 A critical aspect in the construction of such systems lies in balancing chemical stability with acid-sensitivity.”
Saraiva, C., Praça, C., Ferreira, R., Santos, T., Ferreira, L., & Bernardino, L. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.05.044 · Cited by 1,609 · see citing works
Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases
Soto, C., & Pritzkow, S. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0235-9 · Cited by 1,180 · see citing works
Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease.
Marucci, G., Buccioni, M., Ben, D. D., Lambertucci, C., Volpini, R., & Amenta, F. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108352 · Cited by 1,147 · see citing works
Sonavane, G. S., Tomoda, K., & Makino, K. (2008) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2008.07.004 · Cited by 1,105 · cited 1× · see citing works
“187 For instance, 20 nm AuNPs coated with bovine serum albumin exhibited a striking biodistribution pattern in mice: approximately 41% of the injected AuNPs accumulated in the liver and 1.3% in the spleen on the first day.”
InfluentialHuntington's disease: a clinical review
Roos, R. A. C. (2010) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-5-40 · Cited by 1,049 · cited 1× · see citing works
“97 The underlying pathogenesis is multifactorial, involving toxic protein aggregation, transcriptional dysregulation, mitochondrial dysfunction, and neuroinflammation.”
Spilman, P., Podlutskaya, N., Hart, M. J., Debnath, J., Gorostiza, O., Bredesen, D., Richardson, A., Strong, R., & Galvan, V. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009979 · Cited by 1,033 · cited 1× · see citing works
“76 Wang et al further revealed that in a diabetes-induced AD model, rapamycin suppressed the mTOR/p70S6K pathway, reduced both Aβ and phosphorylated tau levels, and improved mitochondrial function.”
Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders
Islam, M. T. (2016) · Neurological Research · doi:10.1080/01616412.2016.1251711 · Cited by 989 · see citing works
Inflammation in CNS neurodegenerative diseases
Stephenson, J., Nutma, E., van der Valk, P., & Amor, S. (2018) · Immunology · doi:10.1111/imm.12922 · Cited by 966 · see citing works
Current Strategies for Brain Drug Delivery
Dong, X. (2018) · Theranostics · doi:10.7150/thno.21254 · Cited by 954 · cited 1× · see citing works
“42–44 (3) Carrier-mediated transport and cell-penetrating peptide strategies (CPPs): Some nanocarriers exploit transporters for endogenous substrates (eg, glucose, amino acids) or are conjugated with cell-penetrating peptides like TAT or Penetratin to induce nonspecific endocytosis, thus broadening…”
Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson’s disease
Rocha, E. M., Miranda, B. D., & Sanders, L. H. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.04.004 · Cited by 769 · cited 1× · see citing works
“82,83 Clinically, treatment remains largely dependent on small-molecule drugs such as levodopa (L-DOPA), yet these agents are limited by short half-life, poor BBB permeability, and pronounced peripheral side effects, severely constraining their long-term efficacy and safety.”
Targeting Huntingtin Expression in Patients with Huntington’s Disease
Tabrizi, S. J., Leavitt, B. R., Landwehrmeyer, G. B., Wild, E. J., Saft, C., Barker, R. A., Blair, N. F., Craufurd, D., Priller, J., Rickards, H., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1900907 · Cited by 708 · see citing works
Enzyme-responsive nanomaterials for controlled drug delivery
Hu, Q., Katti, P. S., & Gu, Z. (2014) · Nanoscale · doi:10.1039/c4nr04249b · Cited by 683 · cited 1× · see citing works
“141 Si et al reported elevated MMP-9 expression in MPTP and A53T mouse models, which impaired AQP4 polarization and brain lymphatic flow.”
Niikura, K., Matsunaga, T., Suzuki, T., Kobayashi, S., Yamaguchi, H., Orba, Y., Kawaguchi, A., Hasegawa, H., Kajino, K., Ninomiya, T., et al. (2013) · ACS Nano · doi:10.1021/nn3057005 · Cited by 639 · cited 1× · see citing works
“193 Moyano et al (2016) further reported that peptide-or protein-functionalized AuNPs significantly modulated cytokine expression and macrophage polarization under lipopolysaccharide (LPS) stimulation in vitro and in murine models, thereby reshaping immune-response patterns.”
pH-responsive polymer nanoparticles for drug delivery
Deirram, N., Zhang, C., Kermaniyan, S. S., Johnston, A. P. R., & Such, G. K. (2019) · Macromolecular Rapid Communications · doi:10.1002/marc.201800917 · Cited by 531 · cited 1× · see citing works
“130 Additionally, polyelectrolytes such as polyacrylic acid exhibit excellent conformational responsiveness and mucoadhesive properties under acidic conditions, enhancing drug retention and penetration in the nervous system.”
beta-Amyloid aggregation induced by human acetylcholinesterase: inhibition studies.
Bartolini, M., Bertucci, C., Cavrini, V., & Andrisano, V. (2003) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)01514-9 · Cited by 523 · see citing works
Huntington’s Disease: Mechanisms of Pathogenesis and Therapeutic StrategiesPreprint
Jiménez-Sánchez, M., Licitra, F., Underwood, B. R., & Rubinsztein, D. C. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a024240 · Cited by 512 · cited 1× · see citing works
“98 At present, there is no definitive cure, and available therapies are largely symptomatic, providing limited capacity to slow disease progression.”
α-Synuclein misfolding and aggregation: Implications in Parkinson’s disease pathogenesis
Mehra, S., Sahay, S., & Maji, S. K. (2019) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2019.03.001 · Cited by 507 · cited 1× · see citing works
“82,83 Clinically, treatment remains largely dependent on small-molecule drugs such as levodopa (L-DOPA), yet these agents are limited by short half-life, poor BBB permeability, and pronounced peripheral side effects, severely constraining their long-term efficacy and safety.”
BDNF as a Promising Therapeutic Agent in Parkinson’s Disease
Palasz, E., Wysocka, A., Gasiorowska, A., Chalimoniuk, M., Niewiadomski, W., & Niewiadomska, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21031170 · Cited by 504 · see citing works
Mueller-Steiner, S., Zhou, Y.-G., Arai, H., Roberson, E., Sun, B.-G., Chen, J., Wang, X., Yu, G.-Q., Esposito, L., Mucke, L., et al. (2006) · Neuron · doi:10.1016/j.neuron.2006.07.027 · Cited by 466 · cited 1× · see citing works
“151 Cathepsin D, a major lysosomal aspartyl protease, is involved in α-synuclein degradation, and its dysfunction contributes to toxic protein accumulation and neurodegeneration in PD. 152 Given their lesion-specific expression and substrate specificity, Cathepsin-responsive systems have been…”
Drug development in Alzheimer’s disease: the path to 2025
Cummings, J., Aisen, P. S., DuBois, B., Frölich, L., Jack, C. R., Jones, R. W., Morris, J. C., Raskin, J., Dowsett, S. A., & Scheltens, P. (2016) · Alzheimer's Research & Therapy · doi:10.1186/s13195-016-0207-9 · Cited by 459 · see citing works
Graphene quantum dots prevent α-synucleinopathy in Parkinson’s disease
Kim, D., Yoo, J. M., Hwang, H., Lee, J., Lee, S. H., Yun, S. P., Park, M. J., Lee, M., Choi, S., Kwon, S. H., et al. (2018) · Nature Nanotechnology · doi:10.1038/s41565-018-0179-y · Cited by 455 · cited 1× · see citing works
“137 Collectively, ROS-responsive platforms provide powerful mechanisms for targeted drug release and neuroprotection in neurodegenerative disease models.”
In vivo renal clearance, biodistribution, toxicity of gold nanoclusters.
Zhang, X.-D., Wu, D., Shen, X., Liu, P., Fan, F.-Y., & Fan, S.-J. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.03.020 · Cited by 448 · cited 1× · see citing works
“197 In contrast, PEGylated AuNPs experience reduced renal filtration due to protein corona formation, exhibit extended circulation, and gradually accumulate in the liver and spleen.”
Mechanisms of autophagy–lysosome dysfunction in neurodegenerative diseases
Nixon, R. A., & Rubinsztein, D. C. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00757-5 · Cited by 435 · cited 2× · see citing works
“166,167 A recent study developed a TPP-functionalized MoS 2 nanocomposite system with catalase and superoxide dismutase mimetic activities, which effectively scavenged ROS in AD models.”
Ehrnhoefer, D. E., Duennwald, M. L., Markovic, P., Wacker, J. L., Engemann, S., Roark, M., Legleiter, J. A., Marsh, J., Thompson, L. M., Lindquist, S. L., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl210 · Cited by 417 · cited 1× · see citing works
“108 Building on this, Cano et al encapsulated EGCG in PEGylated PLGA nanoparticles, which significantly increased its accumulation in the striatum of 3-nitropropionic acid-induced HD mice, reduced mHTT-associated pathology, and improved motor deficits.”
Mathew, A., Fukuda, T., Nagaoka, Y., Hasumura, T., Morimoto, H., Yoshida, Y., Maekawa, T., Venugopal, K., & Kumar, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032616 · Cited by 399 · cited 1× · see citing works
“62 More recently, Saleh et al engineered Tet-1-PLGA platforms to deliver small flavonoids like berberine and isoflavones, which alleviated tau pathology and cognitive deficits in AD models.”
Levodopa therapy for Parkinson's disease: Pharmacokinetics and pharmacodynamics
LeWitt, P. A. (2015) · Movement Disorders · doi:10.1002/mds.26082 · Cited by 379 · see citing works
Alzheimer's DiseasePreprint
Selkoe, D. J. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a004457 · Cited by 371 · cited 1× · see citing works
“58 Given that Aβ primarily accumulates in the brain parenchyma, and most conventional agents fail to cross the BBB effectively, developing nanocarriers that specifically target and eliminate Aβ has become a critical therapeutic strategy.”
Walczak, Ł. J., & Herbet, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179290 · Cited by 351 · cited 1× · see citing works
“140 These enzymes are critically involved in inflammation regulation, phagocytosis, autophagy, and pathological protein degradation, making them ideal “pathological microenvironmental triggers” for designing enzyme-responsive delivery systems.”
Loureiro, J. A., Andrade, S., Duarte, A., Neves, A. R., Queiroz, J. F., Nunes, C., Sevin, E., Fénart, L., Gosselet, F., Coelho, M. A. N., et al. (2017) · Molecules · doi:10.3390/molecules22020277 · Cited by 342 · see citing works
Cano, A., Ettcheto, M., Chang, J.-H., Barroso, E., Espina, M., Kühne, B. A., Barenys, M., Auladell, C., Folch, J., Souto, E. B., et al. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.03.010 · Cited by 337 · cited 1× · see citing works
“170 These pH-triggered, lysosome-targeted nanoplatforms in addition to improved drug delivery efficiency and bioavailability in the brain but also effectively restored the lysosome-autophagy axis, facilitating the clearance of pathological proteins such as Aβ and phosphorylated tau.”
Nanobody: outstanding features for diagnostic and therapeutic applications
Salvador, J., Vilaplana, L., & Marco, M. (2019) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-019-01633-4 · Cited by 317 · see citing works
Álvarez, A., Opazo, C., Alarcón, R., Garrido, J., & Inestrosa, N. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1245 · Cited by 308 · see citing works
Sevlever, D., Jiang, P., & Yen, S.-H. C. (2008) · Biochemistry · doi:10.1021/bi800699v · Cited by 305 · cited 5× · see citing works
“The progressive loss of dopaminergic neurons in the substantia nigra underlies the motor deficits characteristic of PD. 93 These NTFs activate signaling pathways including PI3K/Akt and MAPK/ERK to inhibit neuronal apoptosis, promote axonal regeneration, and sustain synaptic integrity.”
InfluentialCui, G.-H., Guo, H.-D., Li, H., Zhai, Y., Gong, Z.-B., Wu, J., Liu, J.-S., Dong, Y.-R., Hou, S.-X., & Liu, J.-R. (2019) · Immunity & Ageing · doi:10.1186/s12979-019-0150-2 · Cited by 305 · cited 1× · see citing works
“59,60 A diverse range of nanoplatforms has been employed to deliver Aβ-interfering agents.”
García‐Ayllón, M. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00022 · Cited by 303 · cited 1× · see citing works
“146 Other proteases, such as Cathepsin B/D and Asparagine Endopeptidase (AEP), also play vital roles in disease pathology, including autophagy imbalance and pathogenic protein processing.”
Role of dopamine in the pathophysiology of Parkinson’s disease
Zhou, Z.-D., Yi, L.-X., Wang, D. Q., Lim, T. M., & Tan, E.-K. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00378-6 · Cited by 287 · cited 1× · see citing works
“81 Beyond the classical mechanism of neuro-transmitter deficiency, PD pathogenesis involves multifactorial pathological processes, including abnormal aggregation of α-synuclein, neuroinflammatory responses, oxidative stress, and mitochondrial dysfunction.”
Antisense oligonucleotides in therapy for neurodegenerative disorders
Evers, M. M., Toonen, L. J. A., & van Roon‐Mom, W. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.03.008 · Cited by 284 · see citing works
Ashok, A., Andrabi, S. S., Mansoor, S., Kuang, Y., Kwon, B. K., & Labhasetwar, V. D. (2022) · Antioxidants · doi:10.3390/antiox11020408 · Cited by 262 · see citing works
Qie, Y., Yuan, H., Roemeling, C. A. V., Chen, Y., Liu, X., Shih, K. D., Knight, J. A., Tun, H. W., Wharen, R. E., Jiang, W., et al. (2016) · Scientific Reports · doi:10.1038/srep26269 · Cited by 259 · cited 1× · see citing works
“195 Lastly, La-Beck et al systematically analyzed the effects of nanoparticle size, charge, and shape on complement activation, identifying complement activation-related pseudoallergy as a notable clinical risk requiring careful evaluation in translational settings.”
Acetylcholinesterase inhibitors as disease-modifying therapies for Alzheimer's disease.
Muñoz-Torrero, D. (2008) · Current Medicinal Chemistry · doi:10.2174/092986708785909067 · Cited by 241 · cited 1× · see citing works
“138 144 These complexes induce oxidative stress, mitochondrial dysfunction, and inflammation, ultimately exacerbating neuronal apoptosis.”
TDP-43 condensation properties specify its RNA-binding and regulatory repertoire
Hallegger, M., Chakrabarti, A. M., Lee, F. C. Y., Lee, B. L., Amalietti, A. G., Odeh, H. M., Copley, K. E., Rubien, J. D., Portz, B., Kuret, K., et al. (2021) · Cell · doi:10.1016/j.cell.2021.07.018 · Cited by 240 · see citing works
Levodopa in Parkinson’s Disease: Current Status and Future Developments
Tambasco, N., Romoli, M., & Calabresi, P. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170510143821 · Cited by 236 · cited 1× · see citing works
“84 Hence, there is an urgent need to develop more precise, efficient, and brain-targeted drug delivery systems.”
The landscape of nanoparticle-based siRNA delivery and therapeutic development
Moazzam, M., Zhang, M., Hussain, A., Yu, X., Huang, J., & Huang, Y. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.01.005 · Cited by 230 · cited 1× · see citing works
“19,20 By fine-tuning particle size, surface charge, and functional moieties, they can be optimized for the efficient delivery of small molecules, proteins, peptides, and nucleic acids such as siRNA and ASOs.”
Ren, C., Li, D., Zhou, Q., & Hu, X. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119752 · Cited by 228 · cited 1× · see citing works
“168 In parallel, additional research has explored the encapsulation of coenzyme NAD + , antioxidant enzymes, and mitochondrial biogenesis-promoting molecules within TPP-modified platforms to achieve multi-pathway synergistic interventions.”
Treatment of a Mouse Model of ALS by In Vivo Base Editing
Lim, C. K. W., Gapinske, M., Brooks, A. K., Woods, W. S., Powell, J. E., C., M. A. Z., Winter, J., Pérez‐Piñera, P., & Gaj, T. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.01.005 · Cited by 225 · cited 1× · see citing works
“171 Wu et al further used CRISPR-Cas9 to knock out mutant SOD1, observing a marked reduction in spinal cord mutant protein expression, evident neuroprotection, and an approximately 25% increase in lifespan relative to controls.”
Yang, L., Kuang, H.-J., Zhang, W., Aguilar, Z., Wei, H., & Xu, H.-Y. (2017) · Scientific Reports · doi:10.1038/s41598-017-03015-1 · Cited by 219
Nanobiotechnology-based strategies for crossing the blood-brain barrier.
Jain, K. (2012) · Nanomedicine · doi:10.2217/nnm.12.86 · Cited by 207 · cited 1× · see citing works
“41 (2) Receptor-mediated transcytosis: Currently the most widely adopted and efficient brain-targeting mechanism, RMT utilizes the conjugation of specific ligands—such as transferrin, lactoferrin, insulin, ApoE, or Rabies Virus Glycoprotein (RVG) peptides—on the nanocarrier surface.”
In Vivo Study of Spherical Gold Nanoparticles: Inflammatory Effects and Distribution in Mice
Chen, H., Dorrigan, A., Saad, S., Hare, D., Cortie, M., & Valenzuela, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058208 · Cited by 205 · cited 1× · see citing works
“192 Following intravenous administration, AuNPs predominantly accumulate in the liver and spleen, induce elevated levels of inflammatory cytokines (TNF-α, IL-1β, IL-6), and provoke mild local macrophage infiltration, suggesting an inherent risk of in vivo inflammation.”
Design of PLGA-functionalized quercetin nanoparticles for potential use in Alzheimer’s disease
Sun, D., Li, N., Zhang, W., Zhao, Z., Mou, Z., Huang, D., Liu, J., & Wang, W. (2016) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2016.08.052 · Cited by 199 · cited 1× · see citing works
“74 Ginkgolide has similarly demonstrated potent anti-inflammatory and neuroprotective effects by suppressing NF-κB activation.”
New Avenues for the Treatment of Huntington’s Disease
Kim, A. M., Lalonde, K. M., Truesdell, A., Welter, P. G., Brocardo, P. S., Rosenstock, T. R., & Gil‐Mohapel, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168363 · Cited by 198 · see citing works
Faculty of 1000 evaluation for GDNF, NGF and BDNF as therapeutic options for neurodegeneration.
Nairn, A. (2016) · doi:10.3410/f.720339094.793526450 · Cited by 187
Singh, N., Bhardwaj, V., Ravi, C., Ramesh, N., Mandal, A., & Khan, Z. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00244 · Cited by 186 · cited 2× · see citing works
“166,167 A recent study developed a TPP-functionalized MoS 2 nanocomposite system with catalase and superoxide dismutase mimetic activities, which effectively scavenged ROS in AD models.”
In vivo genome editing improves motor function and extends survival in a mouse model of ALS
Gaj, T., Ojala, D. S., Ekman, F. K., Byrne, L. C., Limsirichai, P., & Schaffer, D. V. (2017) · Science Advances · doi:10.1126/sciadv.aar3952 · Cited by 185 · see citing works
Lipid nanoparticles for intranasal administration: application to nose-to-brain delivery
Battaglia, L., Panciani, P., Muntoni, E., Capucchio, M., Biasibetti, E., Bonis, P. D., Mioletti, S., Fontanella, M., & Swaminathan, S. (2018) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2018.1429401 · Cited by 185 · cited 1× · see citing works
“87 For instance, Tang et al designed nanoparticles co-modified with lactoferrin and borneol, achieving efficient intranasal delivery of dopamine and improving motor performance in PD model rats.”
Re, F., Cambianica, I., Zona, C., Sesana, S., Gregori, M., Rigolio, R., Ferla, B. L., Nicotra, F., Forloni, G., Cagnotto, A., et al. (2011) · Nanomedicine: Nanotechnology, Biology and Medicine · doi:10.1016/j.nano.2011.05.004 · Cited by 177 · cited 1× · see citing works
“61 Studies have demonstrated that curcumin-loaded PLGA nanoparticles exhibit pronounced cerebral accumulation, reduce Aβ plaque burden, and improve learning and memory in AD mouse models.”
Mitochondrial Dysfunction: Pathophysiology and Mitochondria-Targeted Drug Delivery Approaches
Khan, T., Waseem, R., Zehra, Z., Aiman, A., Bhardwaj, P., Ansari, J., Hassan, M. I., & Islam, A. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14122657 · Cited by 171 · cited 1× · see citing works
“163 To achieve mitochondrial-specific therapy, researchers have developed active targeting strategies based on mitochondrial membrane potential differences.”
HOOK, V. Y. H., Yoon, M. C., Mosier, C., Ito, G., Podvin, S., Head, B. P., Rissman, R. A., O’Donoghue, A. J., & Hook, G. (2020) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2020.140428 · Cited by 170 · see citing works
Huang, N., Lü, S., Liu, X., Zhu, J., Wang, Y., & Liu, R. (2017) · Oncotarget · doi:10.18632/oncotarget.20944 · Cited by 170 · cited 2× · see citing works
“21 In Alzheimer’s disease mouse models, this system significantly improved spatial learning and memory, reduced Aβ plaque burden and neuroinflammation, thereby demonstrating promising potential in multi-targeted therapeutic interventions.”
SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity
Berdyński, M., Miszta, P., Safranow, K., Andersen, P., Morita, M., Filipek, S., Żekanowski, C., & Kuźma-Kozakiewicz, M. (2022) · Scientific Reports · doi:10.1038/s41598-021-03891-8 · Cited by 162 · cited 1× · see citing works
“International Journal of Nanomedicine 2025:20 https://doi.org/10.2147/IJN.S549893 11027 120–122 RNA-based therapeutic strategies, including siRNAs, ASOs, and CRISPR/Cas9 systems, have been extensively investigated for their potential to silence these pathogenic genes.”
InfluentialWang, P., Zheng, X., Guo, Q., Yang, P., Pang, X., Qian, K., Lü, W., Zhang, Q., & Jiang, X. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.04.034 · Cited by 162 · cited 1× · see citing works
“73 In targeting inflammation and oxidative stress, natural polyphenolic compounds such as quercetin, ginkgolide, and rapamycin have garnered significant attention due to their multifunctional properties, including ROS scavenging, inhibition of microglial activation, and regulation of mTOR/NF-κB…”
Li, X., Wang, B., Zhou, S., Chen, W., Chen, H., Liang, S., Zheng, L., Yu, H., Chu, R., Wang, M., et al. (2020) · Journal of Nanobiotechnology · doi:10.1186/s12951-020-00599-1 · Cited by 161 · cited 1× · see citing works
“199 These findings suggest that ultrasmall clusters favor rapid renal excretion, whereas surface-modified particles, while offering prolonged circulation, heighten the risk of hepatic and splenic retention and chronic toxicity.”
Ballance, W. C., Qin, E. C., Chung, H. J., Gillette, M. U., & Kong, H. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119292 · Cited by 156 · cited 1× · see citing works
“135 Several studies have confirmed the efficacy of ROS-responsive systems in PD models.”
Current State and Future Directions in the Therapy of ALS
Tzeplaeff, L., Wilfling, S., Requardt, M. V., & Herdick, M. L. (2023) · Cells · doi:10.3390/cells12111523 · Cited by 150 · see citing works
Tang, S.-N., Wang, A.-P., Yan, X., Chu, L., Yang, X., Song, Y., Sun, K.-X., Yu, X., Liu, R.-X., Wu, Z., et al. (2019) · Drug Delivery · doi:10.1080/10717544.2019.1636420 · Cited by 144 · cited 1× · see citing works
“88 Inhibition of α -Synuclein Aggregation and Gene Regulation α-Synuclein (α-syn) is a key pathogenic protein in PD, whose abnormal aggregation into Lewy bodies is considered a principal source of neurotoxicity.”
Nanoparticle-Induced Complement Activation: Implications for Cancer Nanomedicine
La-Beck, N. M., Islam, M. R., & Markiewski, M. M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.603039 · Cited by 139 · cited 1× · see citing works
“196”
Yang, X., Yang, W., Xia, X., Lei, T., Yang, Z., Jia, W., Zhou, Y., Cheng, G., & Gao, H. (2022) · Small · doi:10.1002/smll.202203182 · Cited by 135 · cited 1× · see citing works
“184 These responsive designs enhance local drug bioavailability while minimizing off-target toxicity, representing a key strategy for clinical translation of theranostic systems.”
Jiang, S., Cai, G., Yang, Z., Shi, H., Zeng, H., Ye, Q., Hu, Z., & Wang, Z. (2024) · ACS Nano · doi:10.1021/acsnano.3c13150 · Cited by 133 · cited 1× · see citing works
“30 This system modulated microglial polarization in AD mouse models, reduced Aβ plaque deposition, alleviated inflammation, and signifi - cantly improved cognitive performance, demonstrating synergistic advantages in multi-target genetic interventions.”
The blood-brain barrier: Bottleneck in brain drug development
Pardridge, W. M. (2005) · Neurotherapeutics · doi:10.1007/bf03206638 · Cited by 128 · see citing works
Möller, K., Müller, K., Engelke, H., Bräuchle, C., Wagner, E., & Bein, T. (2015) · Nanoscale · doi:10.1039/c5nr06246b · Cited by 128 · see citing works
Jakic, K., Selc, M., Razga, F., Nemethova, V., Mazancová, P., Havel, F., Šrámek, M., Zarska, M., Proska, J., Masanova, V., et al. (2024) · International Journal of Nanomedicine · doi:10.2147/ijn.s443168 · Cited by 126 · cited 1×
“188 Comparative studies have further characterized the in vivo distribution and toxicological profiles of AgNPs and AuNPs following repeated intravenous administration.”
Godinho, B. M. D. C., Ogier, J. R., Darcy, R., O’Driscoll, C. M., & Cryan, J. F. (2013) · Molecular Pharmaceutics · doi:10.1021/mp3003946 · Cited by 126 · see citing works
Neurodegenerative Diseases: From Molecular Basis to Therapy
Agnello, L., & Ciaccio, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112854 · Cited by 121 · cited 1× · see citing works
“For instance, Wang et al developed a biomimetic vesicle platform derived from cell membranes that co-delivers BACE1-targeted siRNA and a plasmid encoding the Triggering Receptor Expressed on Myeloid cells 2 (TREM2).”
Mitochondria-lysosome contact site dynamics and misregulation in neurodegenerative diseases
Cisneros, J., Belton, T. B., Shum, G. C., Molakal, C. G., & Wong, Y. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.01.005 · Cited by 121 · cited 1× · see citing works
“166,169 Encouraging experimental results have emerged from nanocarrier-based strategies aimed at restoring lysosomal integrity and promoting the clearance of protein aggregates.”
RVG-peptide-linked trimethylated chitosan for delivery of siRNA to the brain.
Gao, Y.-K., Wang, Z.-Y., Zhang, J.-H., Zhang, Y., Huo, H., Wang, T.-Y., Jiang, T., & Wang, S.-L. (2014) · Biomacromolecules · doi:10.1021/bm401906p · Cited by 121 · cited 1× · see citing works
“59,60 A diverse range of nanoplatforms has been employed to deliver Aβ-interfering agents.”
Si, X.-L., Dai, S.-B., Fang, Y., Tang, J., Wang, Z.-Y., Li, Y.-N., Song, Z., Chen, Y., Liu, Y., Zhao, G.-H., et al. (2023) · Journal of Advanced Research · doi:10.1016/j.jare.2023.03.004 · Cited by 120 · cited 1× · see citing works
“138 144 These complexes induce oxidative stress, mitochondrial dysfunction, and inflammation, ultimately exacerbating neuronal apoptosis.”
The role of the blood–brain barrier during neurological disease and infection
Patabendige, A., & Janigro, D. (2023) · Biochemical Society Transactions · doi:10.1042/bst20220830 · Cited by 119 · see citing works
Zhang, X., Hongmei, Z., Lu, S. Q., & Li, Y. (2011) · Pharmacological Reports · doi:10.1016/s1734-1140(11)70629-6 · Cited by 116 · see citing works
Recent Advances in Drug Therapy for Parkinson's Disease
Murakami, H., Shiraishi, T., Umehara, T., Omoto, S., & Iguchi, Y. (2022) · Internal Medicine · doi:10.2169/internalmedicine.8940-21 · Cited by 114 · see citing works
Monge-Fuentes, V., Mayer, A. B., Lima, M. R., Geraldes, L., Zanotto, L., Moreira, K., Martins, O., Piva, H. L., Felipe, M., Amaral, A., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-94175-8 · Cited by 105 · cited 1× · see citing works
“85,86 Nanocarrier-based delivery systems provide novel solutions for optimizing dopamine replacement therapy.”
Ludolph, A. C., Brettschneider, J., & Weishaupt, J. H. (2012) · Current Opinion in Neurology · doi:10.1097/wco.0b013e328356d328 · Cited by 103 · cited 1× · see citing works
“112 Although riluzole and edaravone have been approved for ALS treatment, their therapeutic benefits are limited and insufficient to meaningfully halt disease progression.”
Guo, Q., Xu, S., Yang, P., Wang, P., Lü, S., Sheng, D., Qian, K., Cao, J., Lü, W., & Zhang, Q. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.01.039 · Cited by 103 · cited 1× · see citing works
“48 Another innovative strategy involves coating nanoparticles with exogenous cell membranes—such as those from red blood cells, stem cells, or neurons—to construct biomimetic systems.”
Ribeiro, T. D. C., Sábio, R. M., Luiz, M. T., Canto‐de‐Souza, L., Fonseca‐Santos, B., da Silva, L. C. C., Fantini, M. C. D. A., Planeta, C. S., & Chorilli, M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14091976 · Cited by 101 · cited 1× · see citing works
“29 In AD model mice, a single implantation enabled sustained drug release for six weeks, significantly improved cognitive function, and reduced both Aβ deposition and oxidative stress, validating the system’s potential for long-term disease management.”
Nanomedicine for the Treatment of Alzheimer’s Disease
Gregori, M., Masserini, M., & Mancini, S. (2015) · Nanomedicine · doi:10.2217/nnm.14.206 · Cited by 99 · cited 1× · see citing works
“12,13 Compared to conventional formulations, nanocarriers can cross the BBB via various mechanisms such as adsorptive-mediated transcytosis (AMT) and receptor-mediated transcytosis (RMT), enabling passive or active targeting to diseased regions and enhancing local drug concentrations.”
Treatment of Alzheimer’s diseases using donepezil nanoemulsion: an intranasal approach
Kaur, A., Nigam, K., Bhatnagar, I., Sukhpal, H., Awasthy, S., Shankar, S., Tyagi, A. K., & Dang, S. (2020) · Drug Delivery and Translational Research · doi:10.1007/s13346-020-00754-z · Cited by 96 · see citing works
Feng, Q., Zhang, X., Zhao, X., Liu, J., Wang, Q., Yao, Y., Xiao, H., Zhu, Y., Zhang, W., & Wang, L. (2024) · Small · doi:10.1002/smll.202405781 · Cited by 95 · see citing works
Sela, M., Poley, M., Mora‐Raimundo, P., Kagan, S., Avital, A., Kaduri, M., Chen, G., Adir, O., Rozencweig, A., Weiss, Y., et al. (2023) · Advanced Materials · doi:10.1002/adma.202304654 · Cited by 94 · cited 1× · see citing works
“25 In recent years, diverse strategies have been developed to inhibit α-syn aggregation and regulate its expression.”
Pinto, M., Silva, V., Barreiro, S., Silva, R. V. D. S., Remião, F., Borges, F., & Fernandes, C. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101658 · Cited by 94 · cited 1× · see citing works
“19,20 By fine-tuning particle size, surface charge, and functional moieties, they can be optimized for the efficient delivery of small molecules, proteins, peptides, and nucleic acids such as siRNA and ASOs.”
Matrix Metalloproteinases as New Targets in Alzheimer’s Disease: Opportunities and Challenges
Zipfel, P., Rochais, C., Baranger, K., Rivera, S., & Dallemagne, P. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00352 · Cited by 94 · cited 1× · see citing works
“127 Compared with conventional delivery systems, these platforms enable precise on-site drug release within diseased tissues, significantly enhancing targeting efficiency and local therapeutic effects while minimizing systemic toxicity.”
Kordower, J., Isacson, O., & Emerich, D. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7156 · Cited by 91 · see citing works
Engineered pH-Responsive Mesoporous Carbon Nanoparticles for Drug Delivery
Gisbert-Garzarán, M., Berkmann, J., Giasafaki, D., Lozano, D., Spyrou, K., Manzano, M., Steriotis, T., Duda, G., Schmidt-Bleek, K., Charalambopoulou, G., et al. (2020) · ACS Applied Materials and Interfaces · doi:10.1021/acsami.0c01786 · Cited by 89 · cited 1× · see citing works
“132 Although the model in the present study was not specific to neurological diseases, the design concept holds broad translational relevance for CNS-targeted delivery.”
Manap, A. S. A., Tan, A. C. W., Leong, W. H., Chia, A. Y. Y., Vijayabalan, S., Arya, A., Wong, E. H., Rizwan, F., Bindal, U., Koshy, S., et al. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00206 · Cited by 88 · see citing works
Wang, Q., Cheng, S., Qin, F., Fu, A., & Fu, C. (2021) · RSC Advances · doi:10.1039/d1ra00550b · Cited by 85 · cited 1× · see citing works
“178 Furthermore, in the realm of CRISPR-mediated gene editing, AAV9-CasRx/HTT gRNA systems enabled precise knockdown of mHTT RNA in HD knock-in pig models, markedly reducing mutant protein levels and restoring neuronal function, thereby underscoring the effectiveness and clinical promise of…”
Li, J., Wei, Y., Zhang, C., Bi, R., Qiu, Y., Li, Y., & Hu, B. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020621 · Cited by 85 · cited 1× · see citing works
“49 Together, these mechanisms constitute the foundational strategies by which nanomedicines traverse the BBB.”
Morelli, K. H., Wu, Q., Gosztyla, M. L., Liu, H.-S., Yao, M.-M., Zhang, C.-C., Chen, J.-X., Marina, R. J., Lee, K.-H., Jones, K. L., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01207-1 · Cited by 83 · see citing works
Sava, V., Fihurka, O., Khvorova, A., & Sanchez-Ramos, J. (2019) · Nanomedicine: Nanotechnology, Biology and Medicine · doi:10.1016/j.nano.2019.102119 · Cited by 83 · cited 1× · see citing works
“110 Likewise, Zhang et al developed a cyclodextrin-modified nanoplatform with optimized surface functionality to enhance siRNA delivery efficiency into neural cells, achieving potent suppression of mutant HTT expression.”
δ-secretase in neurodegenerative diseases: mechanisms, regulators and therapeutic opportunities
Zhang, Z., Tian, Y., & Ye, K. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-019-0179-3 · Cited by 81 · cited 1× · see citing works
“153,154 Activated by acidic lysosomal pH and inflammatory mediators such as C/EBPβ, AEP cleaves APP and Tau into highly aggregation-prone fragments, promoting plaque and tangle formation in AD.”
Pharmacokinetics, Biodistribution, and Biosafety of PEGylated Gold Nanoparticles In Vivo
Kozics, K., Šramková, M., Kopecka, K., Begerova, P., Manova, A., Krivosikova, Z., Ševčíková, Z., Liskova, A., Rollerova, E., Dubaj, T., et al. (2021) · Nanomaterials · doi:10.3390/nano11071702 · Cited by 79
PLGA-PEG-ANG-2 Nanoparticles for Blood–Brain Barrier Crossing: Proof-of-Concept Study
Hoyos-Ceballos, G. P., Ruozi, B., Ottonelli, I., da Ros, F., Vandelli, M., Forni, F., Daini, E., Vilella, A., Zoli, M., Tosi, G., et al. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12010072 · Cited by 77 · see citing works
Liu, P., Wang, Z.-H., Kang, S. S., Liu, X., Xia, Y., Chan, C.-B., & Ye, K. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01600-z · Cited by 77 · cited 1× · see citing works
“155,156 In PD models, AEP cleaves α-synuclein into toxic fragments, facilitating Lewy body formation and neuronal damage.”
Zhang, Y., & Pardridge, W. (2009) · Pharmaceutical Research · doi:10.1007/s11095-008-9815-9 · Cited by 66 · cited 1× · see citing works
“94 Chen et al further advanced this strategy by combining it with ultrasound-targeted microbubble destruction to enhance delivery efficiency.”
Kuang, Y., Zhang, J., Xiong, M., Zeng, W., Lin, X., Yi, X., Luo, Y., Yang, M., Li, F., & Huang, Q. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.614906 · Cited by 64 · see citing works
Storage of gold nanoclusters in muscle leads to their biphasic in vivo clearance.
Zhang, X.-D., Luo, Z.-T., Chen, J., Wang, H., Song, S.-S., Shen, X., Long, W., Sun, Y.-M., Fan, S.-J., Zheng, K.-Y., et al. (2014) · Small · doi:10.1002/smll.201402233 · Cited by 63 · cited 1×
“200 Accordingly, nanomedicine design should balance pharmacokinetic optimization with long-term safety: For rapid clearance, particles 6 nm with stable surface modifications are preferred.”
Descriptive Epidemiology of Neurodegenerative Diseases: What Are the Critical Questions?
Logroscino, G., Urso, D., & Savica, R. (2022) · Neuroepidemiology · doi:10.1159/000525639 · Cited by 61 · see citing works
Dopamine receptor agonists for Parkinson's disease
Blandini, F., & Armentero, M. (2014) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2014.869209 · Cited by 61 · cited 1× · see citing works
“85,86 Nanocarrier-based delivery systems provide novel solutions for optimizing dopamine replacement therapy.”
Moyano, D. F., Liu, Y., Ayaz, F., Hou, S., Puangploy, P., Duncan, B., Osborne, B. A., & Rotello, V. M. (2016) · Chem · doi:10.1016/j.chempr.2016.07.007 · Cited by 59 · cited 2× · see citing works
“193 Moyano et al (2016) further reported that peptide-or protein-functionalized AuNPs significantly modulated cytokine expression and macrophage polarization under lipopolysaccharide (LPS) stimulation in vitro and in murine models, thereby reshaping immune-response patterns.”
Abbas, H., Refai, H., Sayed, N. S. E., Rashed, L., Mousa, M. H., & Zewail, M. (2021) · International journal of pharmaceutics · doi:10.1016/j.ijpharm.2021.121244 · Cited by 58 · see citing works
Dysregulated mitochondrial Ca2+ and ROS signaling in skeletal muscle of ALS mouse model
Zhou, J., Li, A., Li, X., & Yi, J. (2019) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2019.01.024 · Cited by 58 · cited 1× · see citing works
“117 Anti-inflammatory and antioxidant therapies have thus become focal points in ALS research.”
Erythrocyte membrane-coated nanocarriers modified by TGN for Alzheimer's disease.
Gu, J., Yan, C., Yin, S., Wu, H., Liu, C., Xue, A., Lei, X., Zhang, N., & Geng, F. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.12.030 · Cited by 57 · see citing works
Asparagine endopeptidase is an innovative therapeutic target for neurodegenerative diseases
Zhang, Z.-T., Xie, M., & Ye, K. (2016) · Expert opinion on therapeutic targets · doi:10.1080/14728222.2016.1182990 · Cited by 55 · cited 1× · see citing works
“159 This makes AEP an ideal trigger for enzyme-responsive drug delivery systems.”
Deconvoluting the Complexity of Reactive Oxygen Species (ROS) in Neurodegenerative Diseases
Zhou, Y., Zhen, Y.-Q., Wang, G., & Liu, B. (2022) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2022.910427 · Cited by 52 · cited 1× · see citing works
“134 To address this, researchers have developed ROS-responsive nanocarriers utilizing sulfur, selenium, boronate, or thioether oxidation-sensitive linkers to enable selective drug release in high ROS environments.”
Mazibuko, Z., Choonara, Y. E., Kumar, P., du Toit, L. C., Modi, G., Naidoo, D., & Pillay, V. (2015) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.24322 · Cited by 51 · see citing works
Bunk, J., Huarcaya, S. P., Drobny, A., Dobert, J., Walther, L., Rose-John, S., Arnold, P., & Zunke, F. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.581805 · Cited by 49 · see citing works
Cathepsin D as a therapeutic target in Alzheimer’s disease
Domenico, F. D., Tramutola, A., & Perluigi, M. (2016) · Expert opinion on therapeutic targets · doi:10.1080/14728222.2016.1252334 · Cited by 48 · see citing works
Cao, M. C., Cawston, E. E., Chen, G. L., Brooks, C., Douwes, J. E., McLean, D., Graham, E. S., Dragunow, M., & Scotter, E. L. (2022) · BMC Neurology · doi:10.1186/s12883-022-02730-1 · Cited by 47 · cited 1× · see citing works
“114 To overcome these limitations, various nanodelivery platforms have been developed to enhance the stability and delivery efficiency of neurotrophic factors.”
Stimuli-responsive Polymeric nanosystems for therapeutic applications.
Handa, M., Singh, A., Flora, S. S., & Shukla, R. (2021) · Current pharmaceutical design · doi:10.2174/1381612827666211208150210 · Cited by 47 · cited 1× · see citing works
“15 Some advanced platforms also integrate theranostic functionalities, combining therapeutic delivery with imaging modules—such as MRI, PET, or fluorescent probes—for real-time disease monitoring and therapeutic evaluation.”
Lai, C., Chen, Z., Ding, Y., Qian, C., Su, S., Liu, H., Ni, R., & Tang, Z. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.782434 · Cited by 47 · cited 1× · see citing works
“78 Collectively, these findings underscore rapamycin’s therapeutic promise through its coordinated regulation of multiple neurodegenerative mechanisms.”
Silva, R. O., Counil, H., Rabanel, J., Haddad, M., Zaouter, C., Khedher, M. R. B., Patten, S. A., & Ramassamy, C. (2024) · International Journal of Nanomedicine · doi:10.2147/ijn.s449227 · Cited by 47 · cited 1× · see citing works
“65 Exosomes demonstrated superior BBB penetration, brain accumulation, and cognitive improvement.”
Medina, D. X., Chung, E. P., Teague, C. D., Bowser, R. P., & Sirianni, R. W. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00224 · Cited by 47 · cited 1× · see citing works
“119 Collectively, these studies demonstrate that nanodelivery systems provide novel therapeutic avenues for ALS by improving drug stability, targeting efficiency, and CNS bioavailability.”
Yuan, X., Jia, Z., Li, J., Liu, Y., Huang, Y., Gong, Y., Guo, X., Chen, X., Cen, J., & Liu, J. (2021) · Journal of Materials Chemistry B · doi:10.1039/d1tb01290h · Cited by 47 · cited 1× · see citing works
“183 Similarly, Yang et al designed a dual pH/ROS-responsive nanoplatform co-delivering BACE1-siRNA and rapamycin, intranasally administered in AD mice, which simultaneously suppressed β-secretase expression and improved cognitive behavior.”
Yue, P., Miao, W., Gao, L., Zhao, X.-Y., & Teng, J. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00222 · Cited by 46 · cited 1× · see citing works
“95 In recent years, researchers have developed a variety of innovative nanoplatforms to address the challenges of NTF delivery in PD, aiming to enhance both selectivity and safety.”
Self-citationMendonça, M. C. P., Cronin, M. F., Cryan, J. F., & O’Driscoll, C. M. (2021) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2021.11.003 · Cited by 46 · cited 1× · see citing works
“111 The design philosophy of this system emphasized simultaneous optimization of targeting, stability, and cellular uptake, underscoring its strong therapeutic potential and translational viability.”
Pirhaghi, M., Mamashli, F., Moosavi-Movahedi, F., Arghavani, P., Amiri, A., Davaeil, B., Mohammad-Zaheri, M., Mousavi-Jarrahi, Z., Sharma, D., Langel, Ü., et al. (2024) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.3c01167 · Cited by 46 · cited 1× · see citing works
“45–47 (4) Surface modification and functional design: To further enhance brain specificity and nanocarrier stability, strategies incorporating peptide or glycan ligand modifications have been employed to improve selectivity.”
Extralysosomal cathepsin B in central nervous system: Mechanisms and therapeutic implications
Ni, J., Lan, F., Xu, Y., Nakanishi, H., & Li, X. (2022) · Brain Pathology · doi:10.1111/bpa.13071 · Cited by 44 · see citing works
Metal-organic frameworks: A promising option for the diagnosis and treatment of Alzheimer's disease.
Tajahmadi, S., Molavi, H., Ahmadijokani, F., Shamloo, A., Shojaei, A., Sharifzadeh, M., Rezakazemi, M., Fatehizadeh, A., Aminabhavi, T., & Arjmand, M. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.11.002 · Cited by 43 · cited 1× · see citing works
“182 Such integrated systems have demonstrated closed-loop control capabilities—from lesion identification to therapeutic feed-back—in models of AD, PD, and HD, providing highly modular, controllable, and visualized intervention platforms that are shaping the future of theranostic approaches in…”
Saleh, S. R., Abd-Elmegied, A., Madhy, S. A., Khattab, S. N., Sheta, E., Elnozahy, F. Y., Mehanna, R. A., Ghareeb, D. A., & Abdel-Monem, N. M. (2024) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2024.124218 · Cited by 43 · cited 1× · see citing works
“63, 64 These findings validate the efficacy of Tet-1 modification and extend its applicability to diverse therapeutic payloads, paving the way for individualized interventions in neurodegenerative disease.”
Su, I., Chang, H., Wang, H.-C., & Tsai, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155459 · Cited by 43 · see citing works
Shin, H. J., Kim, I. S., Choi, S. G., Lee, K., Park, H., Shin, J., Kim, D., Beom, J., Yi, Y. Y., Gupta, D. P., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00715-x · Cited by 42 · see citing works
Wang, S., Zhou, S., Min, F.-Y., Ma, J.-J., Shi, X., Bereczki, E., & Wu, J. (2014) · Metabolic Brain Disease · doi:10.1007/s11011-014-9528-1 · Cited by 41 · cited 1× · see citing works
“77 Moreover, Lai et al demonstrated in a zinc-induced tau phosphorylation model that rapamycin simultaneously modulates the mTOR and Nrf2/HO-1 pathways, mitigating oxidative stress and inhibiting aberrant tau phosphorylation, thereby exerting significant neuroprotective effects.”
A Promising Approach: Magnetic Nanosystems for Alzheimer’s Disease Theranostics
Chaparro, C. I. P., Simões, B. T., Borges, J. P., Castanho, M. A. R. B., Soares, P. I. P., & Neves, V. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15092316 · Cited by 40 · cited 2× · see citing works
“79 Contemporary theranostic systems are typically constructed using magnetic nanoparticles (eg, Fe ₃ O ₄ ), quantum dots, near-infrared dyes, or PET imaging probes, co-loaded with therapeutic agents to create dual-functional platforms.”
Endosomal-lysosomal dysfunction in metabolic diseases and Alzheimer's disease
de Almeida, M. F., Bahr, B. A., & Kinsey, S. T. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.02.012 · Cited by 40 · see citing works
Lei, L.-M., Tu, Q.-M., Zhang, X., Xiang, S., Xiao, B., Zhai, S., Yu, H., Tang, L., Guo, B., Chen, X.-Z., et al. (2023) · Chemical Engineering Journal · doi:10.1016/j.cej.2023.141606 · Cited by 39 · cited 1× · see citing works
“136 Another study employed graphene quantum dots capable of crossing the blood–brain barrier and inhibiting α-synuclein aggregation, alleviating striatal damage and improving behavioral outcomes in PD mice, highlighting their neuroprotective potential.”
Joshi, A., Singh, V., Gahane, A., & Thakur, A. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00545 · Cited by 39 · cited 1× · see citing works
“102 In R6/2 transgenic HD mice, this system markedly reduced mHTT aggregation in the striatum and significantly improved motor coordination and neuronal morphology, underscoring its therapeutic potential.”
Cano, A. C., Ettcheto, M., Espina, M., Auladell, C., Folch, J., Kühne, B. A., Barenys, M., Sánchez‐López, E., Souto, E. B., García, M. L., et al. (2021) · Nanomedicine · doi:10.2217/nnm-2020-0239 · Cited by 39 · cited 1× · see citing works
“109 This study highlights the feasibility of using nanocarriers to deliver aggregation inhibitors, providing a tangible solution to the pharmacokinetic limitations of traditional small molecules.”
Sukprasansap, M., Chanvorachote, P., & Tencomnao, T. (2017) · Food and Chemical Toxicology · doi:10.1016/j.fct.2017.03.025 · Cited by 38 · see citing works
Rotondo, R., Proietti, S., Perluigi, M., Padua, E., Stocchi, F., Fini, M., Stocchi, V., Volpe, D., & Pandis, M. F. D. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102089 · Cited by 37 · cited 4× · see citing works
“The progressive loss of dopaminergic neurons in the substantia nigra underlies the motor deficits characteristic of PD. 93 These NTFs activate signaling pathways including PI3K/Akt and MAPK/ERK to inhibit neuronal apoptosis, promote axonal regeneration, and sustain synaptic integrity.”
InfluentialC/EBPβ/AEP Signaling Drives Alzheimer’s Disease Pathogenesis
Xiong, J., Zhang, Z., & Ye, K. (2023) · Neuroscience Bulletin · doi:10.1007/s12264-023-01025-w · Cited by 37 · cited 1× · see citing works
“155,156 In PD models, AEP cleaves α-synuclein into toxic fragments, facilitating Lewy body formation and neuronal damage.”
Stansberry, W. M., & Pierchala, B. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1238453 · Cited by 34 · cited 1× · see citing works
“113 However, due to their macromolecular nature, they are rapidly degraded or cleared in vivo and face significant challenges in crossing the blood–cerebrospinal fluid barrier, which compromises their therapeutic efficacy via conventional administration routes.”
Campisi, A., Sposito, G., Pellitteri, R., Santonocito, D., Bisicchia, J., Raciti, G., Russo, C., Nardiello, P., Pignatello, R., Casamenti, F., et al. (2022) · Antioxidants · doi:10.3390/antiox11101863 · Cited by 34 · see citing works
Intralingual and Intrapleural AAV Gene Therapy Prolongs Survival in a SOD1 ALS Mouse Model
Keeler, A. M., Zieger, M., Semple, C., Pucci, L. A., Veinbachs, A., Brown, R. H., Mueller, C., & ElMallah, M. (2019) · Molecular Therapy: Methods & Clinical Development · doi:10.1016/j.omtm.2019.12.007 · Cited by 34 · cited 1× · see citing works
“177 In PD models, siRNA targeting α-synuclein delivered via RVG-modified polymeric or lipid nanoparticles successfully enhanced brain delivery and reduced protein aggregation, exemplifying the efficacy of RVG-based targeting in CNS RNA therapies.”
Buck, A. C., Maarman, G. J., Dube, A., & Bardien, S. (2025) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2025.1563701 · Cited by 34 · cited 1× · see citing works
“161 Take mitochondria, for example—these organelles are central to oxidative phosphorylation, ATP production, and ROS generation, and their dysfunction plays a pivotal role in the pathogenesis of AD, PD, and ALS.”
PET imaging of microglia in Alzheimer's disease using copper-64 labeled TREM2 antibodies
Shojaei, M., Schaefer, R., Schlepckow, K., Kunze, L. H., Struebing, F. L., Brunner, B., Willem, M., Bartos, L. M., Feiten, A., Palumbo, G., et al. (2024) · Theranostics · doi:10.7150/thno.97149 · Cited by 33 · cited 1× · see citing works
“79 Similarly, Shojaei et al developed a 64Cu-labeled TREM2 antibody nanoplatform for PET imaging of microglial activation, enabling early detection of neuroinflam-matory states; 180 while THK-565, a near-infrared II probe, allows for high-resolution visualization of deep-brain plaques.”
Peptides for trans‐blood–brain barrier delivery
Blades, R., Ittner, L., & Tietz, O. (2023) · Journal of labelled compounds & radiopharmaceuticals · doi:10.1002/jlcr.4023 · Cited by 32 · cited 1× · see citing works
“45–47 (4) Surface modification and functional design: To further enhance brain specificity and nanocarrier stability, strategies incorporating peptide or glycan ligand modifications have been employed to improve selectivity.”
Speidell, A. P., Abid, N. B., & Yano, H. (2023) · Biomedicines · doi:10.3390/biomedicines11082275 · Cited by 32 · see citing works
González, L. F., Bevilacqua, L. E., & Naves, R. F. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13122055 · Cited by 30 · cited 1× · see citing works
“162 In both AD and PD, depolarization of mitochondrial membrane potential, disruption of respiratory chain complexes, and excessive ROS production are considered major drivers of neuronal degeneration.”
Brain Delivery of Protein Therapeutics by Cell Matrix‐Inspired Biomimetic Nanocarrier
Huang, J., Fu, Y., Wang, A., Shi, K., Peng, Y., Yao, Y., Yu, R., Gao, J., Feng, J., Jiang, G., et al. (2024) · Advanced Materials · doi:10.1002/adma.202405323 · Cited by 29 · cited 1× · see citing works
“32 This system crossed the BBB and accumulated in diseased regions, significantly delayed motor function decline, and prolonged survival in ALS model mice, providing a novel paradigm for protein-based therapies in neurodegeneration.”
Takeuchi, I., Onaka, H., & Makino, K. (2018) · Bio-medical materials and engineering · doi:10.3233/bme-171723 · Cited by 29
Wen, X., Wang, L.-M., Liu, Z., Liu, Y.-Y., & Hu, J.-Y. (2014) · International Journal of Neuroscience · doi:10.3109/00207454.2013.877014 · Cited by 29 · cited 1× · see citing works
“72 Furthermore, Wang et al engineered a neuron-targeted nanocomposite capable of systemically delivering BACE1 siRNA, successfully traversing the BBB, reducing cerebral Aβ burden, and improving cognitive function.”
Pardridge, W. M. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1276376 · Cited by 29 · see citing works
Zhang, S., Li, M., Li, Y., Yang, S., Wang, J., Ren, X., Wang, X.-H., Bai, L., Huang, J., Geng, Z., et al. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03258-5 · Cited by 28 · cited 1× · see citing works
“165 Moreover, studies have demonstrated that TPP-modified platforms can restore mitochondrial respiratory chain activity, regulate membrane potential, and ameliorate oxidative stress and metabolic imbalance in models of AD and PD. Compared with non-targeted systems, TPP-modified nanoparticles…”
Self-citationStacchiotti, C., di Regnella, S. M., Cinotti, M., Spalloni, A., & Volpe, E. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26083854 · Cited by 28 · cited 1× · see citing works
“14 56 These studies in addition to highlight the multifaceted value of nanomedicine across diverse neurodegenerative disorders but also provide essential experimental foundations for mechanistic refinement and clinical translation.”
Elhabak, M., Salama, A. A. A., & Salama, A. H. (2023) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.122588 · Cited by 27 · cited 1× · see citing works
“131 In an experimental study, Gisbert-Garzarán et al designed a pH-responsive mesoporous carbon nanoparticle system that efficiently released drugs at lysosomal pH (pH 5.0) while remaining stable at physiological pH, thereby significantly enhancing intracellular targeting efficiency.”
InfluentialSmall extracellular vesicles: a novel drug delivery system for neurodegenerative disorders
Pan, R., Chen, D., Hou, L., Hu, R., & Jiao, Z. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1184435 · Cited by 26 · cited 1× · see citing works
“186 As illustrated in Figure 4, these platforms enable simultaneous imaging (via MRI/PET) and therapeutic delivery, while the efficacy of neuroprotection can be validated through immunohistochemical analyses (eg, Iba-1, TNF-α), forming a complete closed-loop pipeline from imaging to pathological…”
Recent Advances in Nucleic Acid-Based Delivery: From Bench to Clinical Trials in Genetic Diseases.
Oliveira, C., Ribeiro, A., Veiga, F., & Silveira, I. (2016) · Journal of Biomedical Nanotechnology · doi:10.1166/jbn.2016.2245 · Cited by 25
Upregulation of Znf179 acetylation by SAHA protects cells against oxidative stress
Wu, C.-C., Lee, P.-T., Kao, T., Chou, S., Su, R.-Y., Lee, Y., Yeh, S.-H., Liou, J., Hsu, T., Su, T., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2018.08.001 · Cited by 25 · see citing works
Jin, L. J., Nie, L., Deng, Y., Khana, G. J., & He, N. (2025) · Cell Proliferation · doi:10.1111/cpr.13804 · Cited by 24 · cited 1× · see citing works
“13,18 This review aims to provide a comprehensive overview of the major types of nanoplatforms currently employed in the treatment of NDs, highlighting their structural features, BBB penetration capabilities, targeting mechanisms, delivery strategies, and therapeutic outcomes across representative…”
NADPH Oxidases in Neurodegenerative Disorders: Mechanisms and Therapeutic Opportunities
Fiadeiro, M. B., Diogo, J. C., Silva, A., Kim, Y., & Cristóvão, A. C. (2024) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0002 · Cited by 24 · cited 1× · see citing works
“126 These features provide a biological foundation and activation mechanism for designing stimuli-responsive nanocarriers with site-specific drug release capabilities.”
RNA-Targeting CRISPR/CasRx system relieves disease symptoms in Huntington’s disease models
Lin, Y., Li, C., Chen, Y., Gao, J., Li, J., Huang, C., Liu, Z., Wang, W., Zheng, X., Song, X., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00794-w · Cited by 24 · cited 1× · see citing works
“179 Collectively, gene delivery platforms that integrate nanomaterials with molecular biology tools provide robust technological support for precise intervention in a range of pathogenic genes implicated in neurodegenerative disorders.”
Daems, N., Verlinden, B., Hoecke, K. V., Cardinaels, T., Baatout, S., Michiels, C., Lucas, S., & Aerts, A. (2020) · Journal of Biomedical Nanotechnology · doi:10.1166/jbn.2020.2928 · Cited by 23 · see citing works
Handa, M., Sanap, S. N., Bhatta, R., Patil, G. P., Palkhade, R., Singh, D. P., & Shukla, R. (2023) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.3c00454 · Cited by 22 · cited 1× · see citing works
“67 Additionally, intranasal delivery has gained attention as a non-invasive route that bypasses first-pass metabolism and exploits the olfactory pathway for direct brain access.”
Choi, E. S., & Shusta, E. V. (2023) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2023.2286371 · Cited by 22 · cited 1× · see citing works
“42–44 (3) Carrier-mediated transport and cell-penetrating peptide strategies (CPPs): Some nanocarriers exploit transporters for endogenous substrates (eg, glucose, amino acids) or are conjugated with cell-penetrating peptides like TAT or Penetratin to induce nonspecific endocytosis, thus broadening…”
Perich, M. P., Palma-Florez, S., Solé, C., Goberna‐Ferrón, S., Samitier, J., Gómez‐Romero, P., Mir, M., & Lagunas, A. (2023) · Nanomaterials · doi:10.3390/nano13192697 · Cited by 22 · see citing works
Pandey, S. K., & Singh, R. K. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.986668 · Cited by 22 · see citing works
Nanotheranostic agents for neurodegenerative diseases
Padmanabhan, P., Palanivel, M., Kumar, A., Máthé, D., Radda, G. K., Lim, K., & Gulyás, B. Z. (2020) · Emerging Topics in Life Sciences · doi:10.1042/etls20190141 · Cited by 22 · cited 1× · see citing works
“16,17 Despite encouraging results from preclinical studies, the clinical translation of NDDSs continues to face significant challenges, including inconsistent delivery efficiency, insufficient biosafety assessments, complex manufacturing processes, and difficulties in large-scale production.”
Chen, X., Guo, X.-F., Hao, S.-S., Yang, T.-J., & Wang, J.-S. (2022) · Arabian Journal of Chemistry · doi:10.1016/j.arabjc.2022.103748 · Cited by 21
Self-citationFUS gene mutation in amyotrophic lateral sclerosis: a new case report and systematic review
Xiao, X., Li, M., Ye, Z., He, X., Wei, J. S., & Zha, Y. (2023) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2023.2272170 · Cited by 20 · cited 1× · see citing works
“International Journal of Nanomedicine 2025:20 https://doi.org/10.2147/IJN.S549893 11027 120–122 RNA-based therapeutic strategies, including siRNAs, ASOs, and CRISPR/Cas9 systems, have been extensively investigated for their potential to silence these pathogenic genes.”
InfluentialLiu, G.-Z., Niu, T.-T., Yu, Q., Xu, B., Li, X., Yuan, B.-Y., Yuan, G.-B., Yang, T., Li, H., & Sun, Y. (2023) · Aging · doi:10.18632/aging.205072 · Cited by 20 · cited 1× · see citing works
“75 Rapamycin, owing to its multifaceted role in autophagy modulation, mTOR pathway inhibition, and antioxidant response, has recently emerged as a promising agent in AD therapy.”
Mitochondria-targeted nanotherapeutics: A new frontier in neurodegenerative disease treatment
Keethedeth, N., & Shenoi, R. A. (2024) · Mitochondrion · doi:10.1016/j.mito.2024.102000 · Cited by 19 · cited 1× · see citing works
“164 For instance, Zhang et al designed a TPP-functionalized nanovesicle system encapsulating ursodeoxycholic acid (UDCA), which demonstrated remarkable efficacy in a PD mouse model.”
Inhibition of asparagine endopeptidase (AEP) effectively treats sporadic Alzheimer’s disease in mice
Qian, Z., Li, B.-W., Meng, X., Liao, J., Wang, G., Li, Y., Luo, Q., & Ye, K.-Q. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01774-2 · Cited by 19 · cited 1× · see citing works
“157,158 Notably, AEP expression is markedly upregulated during the early stages of disease and is regulated by inflammation and oxidative signaling pathways, exhibiting a distinct lesion-specific activation profile.”
Tuominen, R. K., & Renko, J. (2024) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.14042 · Cited by 18 · see citing works
Engineered nanoparticles for the treatment of Alzheimer’s disease
Jia, J., Zhao, S., Zhao, J., & Gao, Y. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1510798 · Cited by 17 · cited 1× · see citing works
“71 In the realm of tau-targeted therapies, studies have reported the use of polyethyleneimine (PEI)-modified liposomes to deliver tau-specific siRNA, resulting in significant reductions in phosphorylated tau expression and cognitive improvement in murine models.”
Shock and awe: unleashing the heat shock response to treat Huntington disease.
Jackrel, M. E., & Shorter, J. (2011) · Journal of Clinical Investigation · doi:10.1172/jci59190 · Cited by 17 · see citing works
Zhai, L., Gao, Y., Yang, H., Wang, H., Liao, B., Cheng, Y., Liu, C., Che, J., Xia, K., Zhang, L., et al. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123345 · Cited by 17 · cited 1× · see citing works
“96 Such multifunctional nanocarriers represent a promising strategy for gene therapy and autophagy modulation in neurodegenerative disease.”
Gao, C., Xiong, R., Zhang, Z., Peng, H., Gu, Y.-K., Xu, W., Yang, W.-T., Liu, Y., Gao, J., & Yin, Y. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00436-7 · Cited by 16 · cited 1× · see citing works
“185 Regarding BBB traversal, membrane-derived hybrid carriers—such as exosome-and cell membrane-coated nanoparticles—as well as RVG/TGN-modified systems, have significantly improved brain-targeting efficiency in AD and PD models, providing cutting-edge technological support for the precise delivery…”
Nanoparticle-based Traditional Chinese Medicine for Immunotherapy in Gastrointestinal Tumors
Peng, L.-J., Liang, Y., Zhang, Q., Guo, X.-N., Gao, Z.-X., & Cui, D. (2025) · Nano Biomedicine and Engineering · doi:10.26599/nbe.2025.9290115 · Cited by 16 · cited 1× · see citing works
“201 Similarly, PEG-coated magnetic nanoparticles loaded with curcumin exhibited excellent biocompatibility and anti-inflammatory effects in neuronal and macrophage models, suggesting that rational surface engineering and drug-loading strategies can enhance therapeutic efficacy while mitigating…”
Abdelmonem, M., Saad, N., Teh, H., Jaaffar, A. M., Ibrahim, M. A., Alhadad, M. A., & Abdullah, C. A. (2024) · Nano Biomedicine and Engineering · doi:10.26599/nbe.2024.9290099 · Cited by 16 · cited 1× · see citing works
“202 Looking ahead, successful clinical translation of nanomedicines will require breakthroughs in material degradability design, in vivo behavior tracking, and comprehensive long-term safety evaluation, coupled with multicenter clinical trials with extended follow-up to validate efficacy and safety.”
Al-Amin, M., Zehravi, M., Sweilam, S. H., Shatu, M. M., Durgawale, T. P., Qureshi, M. S., Durgapal, S., Haque, M. A., Vodeti, R., Panigrahy, U. P., et al. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149693 · Cited by 15 · see citing works
Leyton-Jaimes, M. F., Ivert, P., Hoeber, J., Han, Y., Feiler, A., Zhou, C., Pankratova, S., Shoshan-Barmatz, V., Israelson, A., & Kozlova, E. (2020) · Scientific Reports · doi:10.1038/s41598-020-77578-x · Cited by 14 · cited 1× · see citing works
“115 Similarly, PEG-PLGA nanoparticles have been employed to deliver BDNF and IGF-1 via the intranasal route in ALS models, achieving enhanced accumulation in the brain, improved neuronal survival, and ameliorated motor deficits.”
Jamwal, S., Elsworth, J. D., Rahi, V., & Kumar, P. (2020) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2020.1801424 · Cited by 12 · cited 1× · see citing works
“–176 However, given the intrinsic instability of these nucleic acid agents in vivo, their susceptibility to enzymatic degradation, limited ability to traverse the blood-brain barrier, and low uptake efficiency, nanocarrier-based delivery systems have emerged as essential structural platforms to…”
Application of CPPs for Brain Delivery.
Srimanee, A., Regberg, J., & Langel, Ü. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2806-4_23 · Cited by 12
Rani, A., Saini, V., Patra, P., Prashar, T., Pandey, R. K., Mishra, A., & Jha, H. C. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00368 · Cited by 11 · see citing works
Tang, Y., Song, X., Xiao, M., Wang, C., Zhang, X., Li, P., Sun, S., Wang, D., Wei, W., & Liu, S. (2024) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.4c16337 · Cited by 11 · cited 1× · see citing works
“31 In AD models, these particles simultaneously inhibited Aβ aggregation and tau phosphorylation, alleviated neuronal pathology, and enhanced spatial learning and memory, affirming their potent therapeutic efficacy.”
Development of asparagine endopeptidase inhibitors for treating neurodegenerative diseases
Meng, X., Li, B., Wang, M., Zheng, W., & Ye, K. (2025) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2025.01.009 · Cited by 10 · cited 1× · see citing works
“160 In conclusion, stimuli-responsive nanocarriers that sense pathological microenvironmental signals characteristic of neurodegenerative diseases provide powerful strategies for precise drug delivery. pH-responsive pH-responsive systems leverage the acidic nature of lysosomes and inflammatory…”
Yan, C., Gu, J., Yin, S., Wu, H., Lei, X., Geng, F., Zhang, N., & Wu, X. (2023) · Journal of drug targeting (Print) · doi:10.1080/1061186x.2023.2290453 · Cited by 9 · cited 1× · see citing works
“39”
Ulanova, M., Gloag, L., Bongers, A., Kim, C.-K., Duong, H. T. K., Kim, H. N., Gooding, J., Tilley, R. D., Biazik, J., Wen, W., et al. (2023) · Cells · doi:10.3390/cells12182279 · Cited by 9 · see citing works
Aguiar, B., Alfenim, A. R., Machado, C., Moreira, J., Pinto, M., Otero-Espinar, F. J., Borges, F., & Fernandes, C. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26052146 · Cited by 8 · cited 1× · see citing works
“118 This platform enhanced edaravone’s CNS penetration, increased its accumulation in brain tissues, and bolstered its antioxidant activity, significantly reducing ROS-induced neuronal damage.”
Saleh, S. R., Khamiss, S. E., Madhy, S. A., Khattab, S. N., Sheta, E., Elnozahy, F. Y., Thabet, E. H., Ghareeb, D. A., Awad, D., & El-Bessoumy, A. A. (2024) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2024.125021 · Cited by 8 · see citing works
Naganuma, F., Murata, D., Inoue, M., Maehori, Y., Harada, R., Furumoto, S., Kudo, Y., Nakamura, T., & Okamura, N. (2023) · Molecular Imaging and Biology · doi:10.1007/s11307-023-01843-4 · Cited by 7 · cited 1×
“181 To enhance synergistic functionality, current nanocarriers often employ liposomes, polymeric nanoparticles, metal-organic frameworks (MOFs), or hybrid architectures, aiming to optimize signal intensity, drug stability, and targeting efficiency.”
Stavrides, P. H., Goulbourne, C., Peddy, J., Huo, C., Rao, M.-L., Khetarpal, V., Marchionini, D. M., Nixon, R. A., & Yang, D.-S. (2024) · bioRxiv · doi:10.1101/2024.05.29.596471 · Cited by 6 · cited 1×
“107 Yet these small molecules frequently suffer from poor solubility, low bioavailability, and limited BBB penetration.”
Schlichtmann, B. W., Palanisamy, B. N., Malovic, E., Nethi, S. K., Padhi, P., Hepker, M., Wurtz, J., John, M., Ban, B., Anantharam, V., et al. (2023) · Biomolecules · doi:10.3390/biom13081203 · Cited by 6 · cited 1× · see citing works
“89 The scFvs significantly reduced α-syn expression in the substantia nigra and improved motor functions, underscoring their therapeutic potential in halting PD progression.”
Parviz, G., Güler, E., Hazar-Yavuz, A. N., Yekeler, H. B., Tatar, E., Kocar, F., Şermet, S., Asghar, A., Wang, X., Ikram, F., et al. (2025) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2025.106887 · Cited by 5 · cited 1× · see citing works
“66 Nanoemulsions have also emerged as promising platforms for CNS delivery of donepezil.”
Li, L.-F., Dawson, V., & Dawson, T. M. (2024) · Neuron · doi:10.1016/j.neuron.2024.10.015 · Cited by 4
Roles of C/EBPβ/AEP in Neurodegenerative Diseases
Guo, J., Liu, X., Yang, S.-S., Li, Q., Duan, Y., Zhu, S., Zhou, K., Yan, Y.-Z., & Zeng, P. H. (2025) · Current Topics in Medicinal Chemistry · doi:10.2174/0115680266357822250119172351 · Cited by 1 · cited 1× · see citing works
“153,154 Activated by acidic lysosomal pH and inflammatory mediators such as C/EBPβ, AEP cleaves APP and Tau into highly aggregation-prone fragments, promoting plaque and tangle formation in AD.”
Flagged first, then by citations
2 of the 201 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- [34]Zhi K, Raji B, Nookala AR, et al. PLGA nanoparticle-based formulations to cross the blood-brain barrier for drug delivery: from R&D to cGMP. Pharmaceutics. 2021; 13(4): 500. doi: 10.3390/pharmaceutics13040500 33917577 PMC8067506 · DOI
- [91]Allen SJ, Watson JJ, Shoemark DK, Barua NU, GDNF PNK. NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther. 2013; 138(2): 155– 175. doi: 10.1016/j.pharmthera.2013.01.004 23348013 · DOI · Paper page
- [128]Pichla M, Bartosz G, Stefaniuk I. Sadowska-Bartosz I. pH-responsive redox nanoparticles protect SH-SY5Y cells at lowered pH in a cellular model of Parkinson’s disease. Molecules. 2021; 26(3): 543. doi: 10.3390/molecules26030543 33494255 PMC7864521 · DOI
- [145]Dinamarca MC, Sagal JP, Quintanilla RA, Godoy JA, Arrázola MS, Inestrosa NC. Amyloid-beta-Acetylcholinesterase complexes potentiate neurodegenerative changes induced by the Abeta peptide. Implications for the pathogenesis of Alzheimer’s disease. Mol Neurodegen. 2010; 5: 4. doi: 10.1186/1750-1326-5-4 PMC2823746 20205793 · DOI
Cited by
Sorted by citations
Bhairam, M., Shukla, S., Pande, R., & Gidwani, B. (2026) · OpenNano · doi:10.1016/j.onano.2026.100299 · Cited by 19 · see citing works
Naim, A., Farooqui, A. M., Badruddeen, Khan, M. I., Akhtar, J., Ahmad, A., Ashique, S., & Islam, A. (2026) · Frontiers in Neurology · doi:10.3389/fneur.2026.1792829 · Cited by 12 · see citing works
Polyoxometalates’ Progress for the Treatment of Alzheimer’s Disease
Aureliano, M., Mateus, J., & Rijo, D. M. (2025) · The biochemist · doi:10.3390/biochem5040041 · Cited by 7 · see citing works
“In fact, nanotechnology has emerged as a transformative strategy for precise brain-targeted treatment [91,92].”
Bartusik‐Aebisher, D., Raj, D. R. J., & Aebisher, D. (2026) · Antioxidants · doi:10.3390/antiox15040430 · Cited by 5 · see citing works
Rajkumar, M., Kirubakaran, D., Govindaraj, P., Shanmugarathinam, A., Deepak, P., Rajkumar, P., Uvarajan, D., Uddandrao, V. V. S., Rajendran, M., & Balamurugan, P. (2026) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2026.115612 · Cited by 6 · see citing works
Fang, L., Zhuang, Y., Zhang, M., Yang, D., Zhang, R., Peng, J., & Wang, C. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1706597 · Cited by 5 · see citing works
“The development of diverse nanocarriers—including polymeric nanoparticles, liposomes, inorganic nanomaterials, and biomimetic vectors—has enabled brain-specific drug delivery and localized release via stimulus-responsive nanocarrier platforms (144).”
Roamcharern, N., & Yubolphan, R. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1810486 · Cited by 4 · see citing works
Targeted nanomedicine strategies for Alzheimer’s disease therapy
Ardah, M. T., Yaseen, B. M., Malathi, H., Ray, S., Thyagarajan, R., Shankhyan, A., Eshmetov, R., Ataullaev, Z., & Mishra, M. K. (2026) · Discover Nano · doi:10.1186/s11671-026-04763-8 · Cited by 3 · see citing works
“Over recent decades, the medical use of nanotechnology has accelerated progress in biosensing and controlled delivery [20, 21].”
Kempuraj, D., Shi, H., Truong, T. D., Kong, D., Sharma, A., Babu, P. R. R., Belur, M. G., Kothuru, S. P., Chinnappan, B., Pena, C., et al. (2026) · The Neuroscientist · doi:10.1177/10738584261453915 · Cited by 3 · see citing works
“BBB-penetrating nanotechnology-based drug delivery systems, such as polymeric nanoparticles, liposomes, inorganic nanomaterials, and biomimetic carriers, may provide brain-targeted treatment (Gao et al 2025).”
Kuwar, O. K., Khan, S., Maloo, A., Singh, C., Sharma, M., Maparu, K., Dhingra, M. S., & Sharma, V. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05991-w · Cited by 3 · see citing works
“Adeno-associated virus vectors have successfully restored mitochondrial enzyme function in preclinical models and in other mitochondrial disorders, providing proof-of-concept for PD and HD [117, 118].”
Dhar, I., Bhatt, S., Gupta, S., Singh, S. K., & Dadhich, A. (2026) · Next Nanotechnology · doi:10.1016/j.nxnano.2026.100557 · Cited by 3 · see citing works
Silva, R., Monteiro, J., Ramalho, M. J., Andrade, S., Loureiro, J. A., & Pereira, M. C. (2026) · Pharmaceuticals · doi:10.3390/ph19050685 · Cited by 2 · see citing works
“Nevertheless, the complexity of their design and the clinical translation remain obstacles to overcome [87].”
InfluentialAbdelaziz, A. M., & Eladawy, R. M. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118381 · Cited by 2 · see citing works
Xing, J. F., Mu, K., Xue, Y., Yang, X., Zhang, D., Gao, W., Zhang, T., Yang, S., Wang, R., Zhang, W., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1843978 · Cited by 2 · see citing works
Bartusik-Aebisher, D., Bania, K., George, B., Dynarowicz, K., & Aebisher, D. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15114359 · Cited by 2 · see citing works
Wang, S., Liu, M., Shi, X., Xiong, T., Li, R., Zheng, W., Huang, Q., Nan, Y., & Ai, K. (2026) · 中国科学通报：英文版 · doi:10.1016/j.scib.2026.05.020 · Cited by 2 · see citing works
Pirmoradi, Z., Soti, M., Kohlmeier, K., Shabani, M., & Shahsavari, F. (2025) · Behavioral and Brain Functions · doi:10.1186/s12993-025-00310-0 · Cited by 2
“…models [19, 23] and nanoemulsions have been shown to not only enhance drug accumulation in the brain but also improve therapeutic efficacy [24, 25], no comparative or systematic study have examined nanoemulsion-based quercetin delivery (Que-NE) specifically in ET or in the harmaline…”
Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions
Zorkina, Y., Abramova, O., Zubkov, E., Gurina, O., & Ushakova, V. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27083560 · Cited by 1 · see citing works
“The high interest in these approaches is confirmed by the exponential growth in the number of publications over the past 10–15 years [21,31].”
Al‐allaq, A. A., Hassan, H. A., Hidayet, H. M., Abdulhakeem, A. A., & Ahmad, Z. A.-A. Q. (2026) · Micro · doi:10.3390/micro6030065 · Cited by 1 · see citing works
“Enzyme-responsive nanocarriers enable precise site-specific drug release by using upregulated disease-related enzymes as pathological microenvironmental triggers [131].”
The nano-neuro nexus: smart sensors at the frontier of detecting neurodegeneration
Mehrotra, A., Sood, A., Yadav, S., Raval, A. D., Jyothi, S. R., Sah, A. K., Sharma, C., & Maharana, L. (2026) · Frontiers in Nanotechnology · doi:10.3389/fnano.2026.1843615 · Cited by 1 · see citing works
Beyond the brain barrier: Hybrid nanoparticles orchestrating intelligent neuro-theranostics.
Saxena, S., Kaur, J., Singh, T. G., Kumar, M., & Awasthi, A. (2026) · Advances in Colloid and Interface Science · doi:10.1016/j.cis.2026.103954 · Cited by 1 · see citing works
Babaali, A., Majdrezaei, Z., Javad-Khayat, Y., Fereidooni, S., & Mirzapoor, A. (2026) · Next Nanotechnology · doi:10.1016/j.nxnano.2026.100742
Song, M.-R., Bu, N., Wei, L., & Chen, J. (2026) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2026.1997252
Nose-to-Brain Inorganic Nanosystems for Alzheimer’s Disease Theranostics
González-Pizarro, C., Vitta, Y., & Kogan, M. J. (2026) · Journal of Pharmaceutical and BioTech Industry · doi:10.3390/jpbi3040024
Porwal, M., Malviya, R., Chandra, P., Sridhar, S., Shareef, J., Wadhwa, T., & Balusamy, B. (2026) · Results in Chemistry · doi:10.1016/j.rechem.2026.103919
4D nanoimaging-guided smart therapeutics: spatiotemporal control of disease microenvironments
Sarma, A., Devi, M., Webster, T. J., Kumar, D., Choudhary, N., & Kondaveeti, S. (2026) · RSC Advances · doi:10.1039/d6ra05783g
“This would allow for the creation of nanoparticles that are sensitive to a particular in ammatory biomarker, providing a powerful solution for early detection and treatment of chronic in ammatory diseases.”
Wu, Y.-Q., Wang, M.-K., Li, T.-P., Huang, Z.-H., Wu, M., Sun, T.-T., & Cong, H.-L. (2026) · International Journal of Nanomedicine · doi:10.2147/ijn.s630802
“77,192 This prospect is grounded in the recognition that each framework contributes a parameter that is, in principle, dynamically regulable by the disease microenvironment.”
InfluentialZhang, M., Chen, B., Li, T., Li, X., Sun, J., Li, Q., Jin, M., Gao, Z., Chen, L., & Huang, W. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18091140
“However, carrier design still lacks relatively mature, generalizable approaches comparable to TPP + , NLSs, or pH-responsive materials [113].”
Recent progress of hydrogel-based strategies for CNS drug delivery.
Li, D., Liu, X.-T., & Liu, Y. (2026) · International journal of pharmaceutics · doi:10.1016/j.ijpharm.2026.127453
Li, Y., Pu, K., Li, D.-Q., Zhao, Y.-J., Cai, Q.-X., Zhou, X., Li, S.-Q., Chen, Y., Zhou, Z.-J., & Liu, Y. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103376
Magdum, A. B., Shinde, K., Jadhav, N. K., Koshti, O. A., Walvekar, K. S., Jagtap, M. A., Patil, S., & Nimbalkar, M. (2026) · Journal of Applied Toxicology · doi:10.1002/jat.70418
Gutierrez-Arratia, J. D., Awad, P. S., Schuh, A. F. S., & Cornejo‐Olivas, M. (2026) · Journal of Parkinson s Disease · doi:10.1177/1877718x261478730
“71,72 Current advances in PD genetics have catalyzed a shift toward precision medicine, exempli fi ed by the development of gene-targeted clinical trials focused on pathways involving GBA1 and LRRK2; although these approaches hold considerable promise, signi fi - cant challenges remain regarding…”
Song, K., Gu, X., Sun, N., Xie, R., Chen, Z., Wang, Z., Li, Y., & Meng, L. (2026) · Biology · doi:10.3390/biology15151235
Abdel-Hamed, M. R., Saber, S., Elmorsy, E. A., Elesawy, B. H., Amer, M. M., Abdel-Moneim, A.-M. H., Firgany, A. E. D., Mohamed, E. A., Eltayeb, H., Hassan, A. M., et al. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1901757
“…reviews on organelle-targeted nanomaterials have documented the rapid expansion of strategies for targeting mitochondria, nuclei, and lysosomes, these works are predominantly organized around application-oriented delivery strategies (Buck et al., 2025; Gao L. et al., 2025; Soukar et al., 2025).”
Lazzaro, G. D., Cimmino, A., Bentivoglio, A. R., Stocchi, F., & Calabresi, P. (2026) · Journal of Parkinson's Disease · doi:10.1177/1877718x261431104
“25 – 33 The translational role of animal studies Preclinical studies have demonstrated that CDD can provide sustained dopaminergic stimulation and exert a bene fi cial effect on motor fl uctuations and LIDs as compared to standard oral L-DOPA therapy.”
Chen, F., Wang, L., Liu, H., Khan, Q., Tang, B., & Bao, N. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04551-7
“Owing to their physicochemical properties, compatibility, small size, biodegradability, and customizable surfaces, nanotechnology-based drug delivery approaches hold great promise for the site-specific delivery of therapeutics in neurological disorders, including AD, PD, HD, ALS, and MS [171].”
Kumar, R. R., & Enoch, I. V. (2026) · Lung Cancer · doi:10.1016/j.lungcan.2026.109518
The Potential of Inorganic Nanocarriers in Enhancing the Effectiveness of Ciprofloxacin: Review
Fahrezi, R. I., Prabowo, M. H., & Istikharah, R. (2026) · Next Research · doi:10.1016/j.nexres.2026.102147
Gilani, S., Sultan, A., Alshawwa, S., & Rizwanullah, M. (2026) · International Journal of Nanomedicine · doi:10.2147/ijn.s628279
“181 Mucoadhesive functionalization represents one of the most widely investigated strategies for improving intranasal drug delivery.”
Deng, L., Li, H., Yang, S., Chen, F., Qiao, J., 包慧中, Wang, X., Fang, S., Xu, B., & Tang, Z. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04654-1
“Second, coating nanoparticles with exogenous cell membranes or exosomes (e.g., derived from erythrocytes, stem cells, or neurons) generates biomimetic systems that promote immune evasion and pro-long circulation time [133, 178].”
Targeting phase separation: a new strategy to disrupt the stromal-immune axis in colorectal cancer
Fu, C., Chen, X., Yi, H., Huang, H.-Y., Zhang, L.-P., Huang, H.-N., Jiang, F., Lei, F., Yu, H.-L., Liu, J.-B., et al. (2026) · Cell Communication and Signaling · doi:10.1186/s12964-026-02849-5
“In this manner, nanotechnology has shown potential for pathogenic condensate targeting, especially in the areas of precise drug delivery and minimizing side effects [221], including the use of findings from neurodegenerative disorders [222].”
Byrne, A. J., Pibuel, M. A., Martínez, J. M. L., & Franco, P. G. (2026) · Journal of Neurochemistry · doi:10.1111/jnc.70422
Antisense Oligonucleotides as Precision Therapies for Neurodegenerative Diseases: A Narrative Review
Mohebbi, S., Ghanbari, M., & Hassanlou, M. (2026) · Jentashapir Journal of Cellular and Molecular Biology · doi:10.5812/jjcmb-169275
“…main value lies in improving stability, CNS penetration, cellular uptake, and tissue selectivity, especially when conventional IT delivery is unlikely to provide adequate exposure to deeper or more diffuse disease-relevant regions (34, 35, 38, 39, 40, 42, 47, 48, 49, 50, 52, 53, 54, 55, 56, 57).”
Nanotechnology-Based Drug Delivery Across the Blood-Brain Barrier in Neurodegenerative Diseases
Tariq, A., Khayyam, U., Shah, R., Batool, H., Pervaiz, A., Tabish, S. A., & Samejo, I. K. (2026) · Journal of Health, Wellness and Community Research · doi:10.61919/jyynt917
- Authors
- Gao, L., Wang, J., & Bi, Y.
- Corresponding author
- Bi, Yanhua
- Venue
- International Journal of Nanomedicine
- Publisher
- Informa UK Limited
- Published
- 2025-09
- Volume
- Volume 20
- Pages
- 11015-11044
- ISSN
- 1176-9114 (ISSN-L)
- 1178-2013
- PMC
- PMC12433253
- OpenAlex
- W4414148219
- Cited by
- 52
- References
- 201
- Citations by year
- 2026: 49 · 2025: 3
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Nanomedicine (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- neurodegenerative diseases, brain drug delivery, blood-brain barrier, stimuli-responsive nanocarriers, polymeric nanoparticles, liposomes, inorganic nanomaterials, mitochondrial targeting, lysosomal targeting, subcellular drug delivery, theranostic nanoplatform, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, protein aggregation, mitochondrial dysfunction, neuroinflammation
- MeSH terms
- Nanoparticle Drug Delivery System, Animals, Blood-Brain Barrier, Brain, Drug Carriers, Humans, Liposomes, Organelles, Drug Delivery Systems, Neurodegenerative Diseases, Nanomedicine, Nanoparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
