Highly sensitive Curcumin-conjugated nanotheranostic platform for detecting amyloid-beta plaques by magnetic resonance imaging and reversing cognitive deficits of Alzheimer's disease via NLRP3-inhibition
Open accessAbstract
BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder without effective therapy and lack diagnosis strategy for preclinical AD patients. There is an urgent need for development of both early diagnosis and therapeutic intervention of AD. RESULTS: Herein, we developed a nanotheranostics platform consisting of Curcumin (Cur), an anti-inflammatory molecule, and superparamagnetic iron oxide (SPIO) nanoparticles encapsulated by diblock 1,2-dio-leoyl-sn-glycero-3-phosphoethanolamine-n-[poly(ethylene glycol)] (DSPE-PEG) that are modified with CRT and QSH peptides on its surface. Furthermore, we demonstrated that this multifunctional nanomaterial efficiently reduced β-amyloid plaque burden specifically in APP/PS1 transgenic mice, with the process noninvasively detected by magnetic resonance imaging (MRI) and the two-dimensional MRI images were computed into three-dimension (3D) plot. Our data demonstrated highly sensitive in vivo detection of β-amyloid plaques which more closely revealed real deposition of Aβ than previously reported and we quantified the volumes of plaques for the first time based on 3D plot. In addition, memory deficits of the mice were significantly rescued, probably related to inhibition of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasomes. CONCLUSIONS: Gathered data demonstrated that this theranostic platform may have both early diagnostic and therapeutic potential in AD.
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Oxidative stress and neuroinflammation rank as key secondary targets (10 studies), with Nps incorporating antioxidants or immunosuppressants.
“Oxidative stress and neuroinflammation rank as key secondary targets (10 studies), with Nps incorporating antioxidants (CeNCs, tannic acid, curcumin, quercetin) or immunosuppressants (dexamethasone, cyclophosphamide) to prevent neuronal death and attenuate inflammation [58,70,71,78].”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [58]
The Results and discussion section reports that curcumin-conjugated nanoparticles reduced inflammatory markers in Alzheimer’s-model mice, supporting the curcumin and neuroinflammation portion of the multi-citation sentence. This paper does not establish the stated count of 10 studies or show that its nanoparticles target oxidative stress; it also does not study the other listed compounds. (LLM, conf=0.83)
Experimental — accuracy not yet measuredIn animal models, reduction in amyloid plaque burden, decrease in neuroinflammation and oxidative stress, and improvement in cognitive functions in behavioral tests have been demonstrated.
“In animal models, a reduction in the burden of amyloid plaques [58,68,75], a decrease in neuroinflammation and oxidative stress, as well as an improvement in cognitive functions in behavioral tests [58,64,72,73,83,85] have been demonstrated.”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [58]
The Results and discussion sections report reduced amyloid plaques, lower neuroinflammatory markers (CD68, NLRP3 and IL-18), and improved Morris water maze performance in treated APP/PS1 mice (Figs. 3, 5 and 6; page numbers unavailable). Our copy does not report a demonstrated decrease in oxidative stress, so that part of the attributed claim is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn Ruan et al., histological analysis was performed immediately after the completion of injections, which does not allow judgment on long-term consequences.
“However, histological analysis was performed immediately after the completion of injections, which does not allow judgment on long-term consequences.”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [58]
The Methods (In vivo test in AD mouse model; page unavailable) describe injections every four days for three months, and Tissue preparation says brains were collected after behavioral tests. The Results (SDP@Cur-CRT/QSH ameliorates spatial memory deficits; page unavailable) report histological assessments after three months of treatment, with no post-treatment follow-up described. The copy does not establish that histology was performed immediately after the final injection. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIn Ruan et al., SDP@Cur-CRT/QSH Nps at a dose of 5 mg/kg were used both for MRI visualization of amyloid plaques and for therapy (every 4 days for 3 months).
“SDP@Cur-CRT/QSH Nps at a dose of 5 mg/kg were used both for MRI visualization of amyloid plaques and for therapy (every 4 days for 3 months).”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [58]
The Materials and methods section ('In vivo test in AD mouse model'; page unavailable) reports SDP@Cur-CRT/QSH treatment every four days for three months, but gives the dose as 25 mg/kg, not 5 mg/kg. The separate 'In vivo MRI scan' section describes its use to visualize amyloid plaques and specifies an imaging dose of 200 μmol Fe/kg. (LLM, conf=0.94)
Experimental — accuracy not yet measuredThe only study where two identical doses were administered for therapy and diagnostics in vivo is the work by Ruan et al.
“The only study where two identical doses were administered for therapy and diagnostics in vivo is the work by Ruan and co-authors [58].”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [58]
The Materials and methods sections describe in vivo MRI and therapeutic treatment with the same nanoparticle platform. They report the MRI dose as 200 μmol Fe/kg and the treatment dose as 25 mg/kg, without establishing that the doses were identical. The paper also does not establish that it was the only study to use identical doses for these purposes. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Although individual studies include repeated administration over 1-2 months, the issue of the optimal regimen for chronic therapy is not systematically discussed.
“Although individual studies include repeated administration over 1–2 months [44,58], the issue of the optimal regimen for chronic therapy is not systematically discussed.”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [58]
The Materials and methods section (“In vivo test in AD mouse model”; page unavailable) confirms repeated administration, but specifies injections every four days for three consecutive months, not 1–2 months. The cited paper does not systematically discuss an optimal chronic-treatment regimen, but its reported treatment duration does not match the claim. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn Ruan et al., although the single dose coincides, the cumulative therapeutic dose (>100 mg/kg) exceeds the diagnostic one by 20 times.
“Although the single dose coincides, the cumulative therapeutic dose (>100 mg/kg) exceeds the diagnostic one by 20 times.”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [58]
Materials and methods, ‘In vivo test in AD mouse model’ (page not provided), reports 25 mg/kg every four days for three months, supporting a cumulative therapeutic dose above 100 mg/kg. ‘In vivo MRI scan’ (page not provided) gives the diagnostic dose as 200 μmol Fe/kg, not in the same units. The copy therefore does not establish that the single doses coincide or that the cumulative therapeutic dose is exactly 20 times the diagnostic dose. (LLM, conf=0.88)
Experimental — accuracy not yet measuredA significant portion of studies use MRI with contrast agents based on gadolinium, SPIONs, or manganese ions, reflecting the researchers' desire to create platforms potentially applicable in clinical practice.
“A significant portion of the studies use MRI with contrast agents based on gadolinium [70,71], SPIONs [58,63,73,83], or manganese ions [72], reflecting the researchers’ desire to create platforms potentially applicable in clinical practice.”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [58]
Alternative targeting strategies include peptide ligands targeting hyperphosphorylated tau, BBB penetration property, small molecules binding beta-sheet structure, and electrostatic interactions.
“Alternative strategies include the use of peptide ligands targeting hyperphosphorylated tau protein [64] or the property of penetrating the BBB [58,72], as well as small molecules that bind to the beta-sheet structure of amyloid fibrils [83]. In some works, specificity is achieved through electrostatic interactions between the charged surface of Nps and negatively charged amyloid aggregates [68].”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [58]
In Ruan et al., over 3 months of administration, no changes in body weight or organ histology were detected.
“Over 3 months of administration, the authors did not detect any changes in body weight or organ histology.”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [58]
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“A highly sensitive nanotheranostic platform consisting of curcumin reduced Aβ plaque formation in APP/PS1 mice and rescued memory deficits, which was likely related to inhibition of the NLRP3 inflammasome (Ruan et al., 2022).”
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“Additionally, the mice’s memory deficits were significantly improved, possibly due to the inhibition of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasomes (Ruan et al. 2022 ).”
Decoding NLRP3 Inflammasome Activation in Alzheimer’s Disease: A Focus on Receptor Dynamics
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Non-pharmacological treatment of Alzheimer’s disease: an update
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“Similarly, cognitive deficits of Alzheimer’s disease could be reversed via NLRP3-inhibition [17].”
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“Moreover, by suppressing NLRP3 activation, this platform reverses cognitive impairment caused by AD, offering new therapeutic possibilities (Ruan 2022).”
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“Increased absorption of curcumin derived from turmeric rhizome by constructing curcumin nanomicelles using effective methods such as liposomes showed good results in clinical trials [71].”
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“Additionally, nanocarriers loaded with imaging agents such as curcumin or Aβ antibodies have been developed to image and/or monitor Aβ in the brains [40–42].”
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“20 have con fi rmed that inhibition of NLRP3 in fl ammasomes contributes to alleviate memory de fi cits of AD mice.”
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“Similarly, curcumin-loaded SPIONs encapsulated by DSPE-PEG showed specific binding to transferrin receptors and early amyloid-beta plaques, effectively inhibiting aggregation by suppressing NLRP3 inflammasome activity [114].”
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“72 Cai et al conducted in vivo and in vitro studies to examine the effects of salidroside on AD.”
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“93 Exosomes, as an innovative carrier, can transport curcumin, and their surface inherits speci fi c proteins, such as lymphocyte function-associated antigen 1 (LFA-1), which can speci fi c-ally bind to intercellular adhesion molecule 1 (ICAM-1) on endothelial cells of the BBB.”
Self-citationTSPO in pancreatic beta cells and its possible involvement in type 2 diabetes
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“Based on their findings, this theranostic platform has promise for use in both the diagnosis and treatment of early-stage AD [71].”
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“Changeable surface markers or dose plans can be tailored to each subgroup (141 – 148).”
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“However, curcumin nanoparticles can be viewed as an inexpensive, risk-free, and readily available alternative for AD prevention and treatment [94].”
Noninvasive imaging of amyloid‐beta and tau in rodent and nonhuman primate models
Ni, R., & Rominger, A. (2025) · Open Research (University of Surrey) · doi:10.1002/viw.20250071
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Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions
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“A significant portion of the studies use MRI with contrast agents based on gadolinium [70,71], SPIONs [58,63,73,83], or manganese ions [72], reflecting the researchers’ desire to create platforms potentially applicable in clinical practice.”
InfluentialBegum, M. Y., Rajkumar, M., Govindaraj, P., Prathap, N., Sudha, P. N., Hamod, M. A., Alotaibi, H., & Uvarajan, D. (2026) · Inflammopharmacology · doi:10.1007/s10787-026-02381-5 · Cited by 1 · see citing works
“Ruan et al. (2022) developed a multifunctional nanother-anostic platform that combines curcumin with superpara-magnetic iron oxide nanoparticles to enable simultaneous diagnosis and treatment of AD.”
Toderescu, C. D., Cresneac, I., Oancea, A., Trifunschi, S., Munteanu, M., & Boru, C. (2026) · Applied Sciences · doi:10.3390/app16052620 · Cited by 1 · see citing works
“…Aliakbari (2021) [51] Adequate Direct + Indirect In vitro Halder (2022) [52] Adequate Indirect In vivo Andrade (2022) [53] Adequate Direct In vitro Ruan (2022) [54] Adequate Indirect In vivo Andrade (2023) [55] Adequate Direct In vitro Zhang (2024) [56] Adequate Direct In vitro Mirzaei-Behbahani…”
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Curcumin as a modulator of IL-18: A promising therapeutic approach for inflammatory diseases
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“In the APP/PS1 mouse model, the platform achieved 3D MRI-based quantitative monitoring of Aβ plaque burden and simultaneously exerted neuroprotective and cognitive improving effects through sustained release of curcumin, representing the current pinnacle of theranostic design [85] ( Figure 8D ).”
Developing precision nanoparticle-based drug delivery systems for Alzheimer's disease therapy
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“…(1.23 mm 3 vs 1.73 mm 3 ), attenuation of neuroinflammation (NLRP3/IL-18/CD68 downregulation, p 0.05–0.001), and cognitive recovery in APP/PS1 mice (improved Morris water maze performance), while exhibiting excellent colloidal stability (PDI 0.174–0.245, ζ ≈ −19.3 mV) 124 (Supplementary Table 2).”
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“In addition, it inhibits the microglia-mediated neuroinflammatory response via the NF-κ B/NLRP3 pathway, reducing glial activation and the sustained production of proinflammatory cytokines [60,61].”
AI-powered medicinal chemistry and translational drug development
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Self-citationCurcumin as theranostics: imaging-guided therapeutics in oncology and neurodegenerative diseases
Yasir, M., Maurya, R. K., & Tripathi, A. S. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1790555
“MRI offers superior soft-tissue contrast and anatomical detail, often augmented by superparamagnetic iron oxide nanoparticles (SPIONs/ USPIOs) or gadolinium complexes co-formulated with curcumin (38).”
Zhang, R., Dai, T.-T., Zhu, Z.-M., & Gong, W.-J. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06228-6
Turmeric as a Therapeutic Agent against Arsenic-Induced Metabolic Dysregulation in Rat Models
Adetutu, A., Aborisade, A. B., & Olaniyi, T. (2024) · Pharmacological Research · doi:10.1016/j.prenap.2024.100110
- Authors
- Ruan, Y., Xiong, Y., Fang, W., Yu, Q., Mai, Y., Cao, Z., Wang, K., Lei, M., Xu, J., Liu, Y., Zhang, X., Liao, W., & Liu, J.
- Affiliations
- Second Affiliated Hospital of Guangzhou Medical University (CN)
- Guangzhou First People's Hospital (CN)
- Sun Yat-sen University (CN)
- Harvard University (US)
- Corresponding author
- Zhang, Xingcai
- Liao, Wang
- Liu, Jun
- Venue
- Journal of Nanobiotechnology
- Published
- 2022-07-14
- Volume
- 20
- Issue
- 1
- Pages
- 322-322
- ISSN
- 1477-3155 (ISSN-L)
- PMC
- PMC9281113
- OpenAlex
- W4285389897
- Cited by
- 85
- References
- 59
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 28 · 2023: 23
- FWCI
- 10.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Nanobiotechnology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by)
- Funders
- National Natural Science Foundation of China (82101271, 81870836)
- Natural Science Foundation of Guangdong Province of China (2020A1515110317, 2020A1515010210)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid plaques, curcumin, nanotheranostics, superparamagnetic iron oxide nanoparticles, magnetic resonance imaging, NLRP3 inflammasome inhibition, cognitive impairment, APP/PS1 mice, peptide surface modification, early diagnosis
- MeSH terms
- Theranostic Nanomedicine, NLR Family, Pyrin Domain-Containing 3 Protein, Alzheimer Disease, Animals, Cognition, Curcumin, Disease Models, Animal, Magnetic Resonance Imaging, Mice, Transgenic, Amyloid beta-Peptides, Mice, Plaque, Amyloid
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 ›
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