Pharmacological and toxicological target organelles and safe use of single-walled carbon nanotubes as drug carriers in treating alzheimer disease.
Abstract
Identification of pharmacological and toxicological profiles is of critical importance for the use of nanoparticles as drug carriers in nanomedicine and for the biosafety evaluation of environmental nanoparticles in nanotoxicology. Here we show that lysosomes are the pharmacological target organelles for single-walled carbon nanotubes (SWCNTs) and that mitochondria are the target organelles for their cytotoxicity. The gastrointestinally absorbed SWCNTs were lysosomotropic but also entered mitochondria at large doses. Genes encoding phosphoinositide-3-kinase and lysosomal-associated membrane protein 2 were involved in such an organelle preference. SWCNT administration resulted in collapse of mitochondrial membrane potentials, giving rise to overproduction of reactive oxygen species, leading to damage of mitochondria, which was followed by lysosomal and cellular injury. Based on the dosage differences in target organelles, SWCNTs were successfully used to deliver acetylcholine into brain for treatment of experimentally induced Alzheimer disease with a moderate safety range by precisely controlling the doses, ensuring that SWCNTs preferentially enter lysosomes, the target organelles, and not mitochondria, the target organelles for SWCNT cytotoxicity.From the clinical editor Single wall carbon nanotubes (SWCNT) could make excellent targeted delivery systems for pharmaceuticals. Inside the cells, lysosomes are the pharmacological target organelles of SWCNT, but in large doses mitochondria also take up SWCNT and mitochondrial toxicity becomes the reason for overall toxicity of this approach. In this paper, SWCNT were successfully used to deliver acetylcholine in Alzheimer's disease brains with high safety range by controlling the doses to ensure lysosomal but not mitochondrial targeting.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Acetylcholine loaded in carbon nanotubes restores significant cognitive functions to pre-Alzheimer disease level in a kainic-acid induced mouse model compared to free acetylcholine.
“The ACh loaded in carbon nanotubes have been found to restore the significant cognitive functions to pre-AD level in a kainic-acid induced mouse model as compared to free ACh”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Yang et al., 2010
Cites
Liu, J., Rinzler, A. G., Dai, H., et al. (1998) · Science · doi:10.1126/science.280.5367.1253 · Cited by 2,904 · see citing works
Lam, C.-W. (2003) · Toxicological Sciences · doi:10.1093/toxsci/kfg243 · Cited by 1,992 · see citing works
Smiley, S. T., Reers, M., Mottola-Hartshorn, C., Lin, M., Chen, A. B., Smith, T. W., Steele, G., & Chen, L. B. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.9.3671 · Cited by 1,629 · see citing works
Seglen, P. O., & Gordon, P. B. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.6.1889 · Cited by 1,360 · see citing works
Bae, Y., Fukushima, S., Harada, A., & Kataoka, K. (2003) · Angewandte Chemie International Edition · doi:10.1002/anie.200250653 · Cited by 1,329 · see citing works
Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice
Shvedova, A. A., Kisin, E. R., Mercer, R., Murray, A. R., Johnson, V. J., Potapovich, A. I., Tyurina, Y. Y., Gorelik, O., Arepalli, S., Schwegler-Berry, D., et al. (2005) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00084.2005 · Cited by 1,312 · see citing works
Shvedova, A. A., Castranova, V., Kisin, E. R., Schwegler‐Berry, D., Murray, A. R., Gandelsman, V., Maynard, A., & Baron, P. A. (2003) · Journal of Toxicology and Environmental Health · doi:10.1080/713853956 · Cited by 1,245 · see citing works
Respiratory toxicity of multi-wall carbon nanotubes
Muller, J., Huaux, F., Moreau, N., Misson, P., Heilier, J.-F., Delos, M., Arras, M., Fonseca, A., Nagy, J. B., & Lison, D. (2005) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2005.01.008 · Cited by 1,123 · see citing works
Cellular uptake of functionalized carbon nanotubes is independent of functional group and cell type
Kostarelos, K., Lacerda, L., Pastorin, G., Wu, W., Wieckowski, S., Luangsivilay, J., Godefroy, S., Pantarotto, D., Briand, J., Muller, S., et al. (2007) · Nature Nanotechnology · doi:10.1038/nnano.2006.209 · Cited by 1,111 · see citing works
Pantarotto, D., Briand, J., Prato, M., & Bianco, A. (2003) · Chemical Communications · doi:10.1039/b311254c · Cited by 1,100 · see citing works
Functionalized Carbon Nanotubes for Plasmid DNA Gene Delivery
Pantarotto, D., Singh, R. N., McCarthy, D., Erhardt, M., Briand, J., Prato, M., Kostarelos, K., & Bianco, A. (2004) · Angewandte Chemie International Edition · doi:10.1002/anie.200460437 · Cited by 1,093 · see citing works
The biocompatibility of carbon nanotubes
Smart, S. K., Cassady, A. I., Lu, G. Q., & Martin, D. J. (2006) · Carbon · doi:10.1016/j.carbon.2005.10.011 · Cited by 1,011 · see citing works
Carbon nanotubes as intracellular protein transporters: generality and biological functionality.
Kam, N. W., & Dai, H. (2005) · Journal of the American Chemical Society · doi:10.1021/ja050062v · Cited by 985 · see citing works
Effect of single wall carbon nanotubes on human HEK293 cells
Cui, D., Tian, F., Ozkan, C. S., Wang, M., & Gao, H. (2004) · Toxicology Letters · doi:10.1016/j.toxlet.2004.08.015 · Cited by 825 · see citing works
Near-Infrared Fluorescence Microscopy of Single-Walled Carbon Nanotubes in Phagocytic Cells
Cherukuri, P., Bachilo, S. M., Litovsky, S. H., & Weisman, R. B. (2004) · Journal of the American Chemical Society · doi:10.1021/ja0466311 · Cited by 817 · see citing works
Multi-walled carbon nanotube interactions with human epidermal keratinocytes
Monteiro-Riviere, N. A., Nemanich, R. J., Inman, A. O., Wang, Y. Y., & Riviere, J. E. (2004) · Toxicology Letters · doi:10.1016/j.toxlet.2004.11.004 · Cited by 756 · see citing works
Multi-walled carbon nanotubes induce T lymphocyte apoptosis
Bottini, M., Bruckner, S. R., Nika, K., Bottini, N., Stefano Bellucci, A., Magrini, A., Bergamaschi, A., & Mustelin, T. (2005) · Toxicology Letters · doi:10.1016/j.toxlet.2005.06.020 · Cited by 677 · see citing works
Mitochondria in cancer cells: what is so special about them?
Gogvadze, V. G., Orrenius, S., & Zhivotovsky, B. (2008) · Trends in Cell Biology · doi:10.1016/j.tcb.2008.01.006 · Cited by 636 · see citing works
Direct imaging of single-walled carbon nanotubes in cells
Porter, A. E., Gass, M., Muller, K., Skepper, J. N., Midgley, P. A., & Welland, M. (2007) · Nature Nanotechnology · doi:10.1038/nnano.2007.347 · Cited by 564 · see citing works
Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: Role of iron
Kagan, V. E., Tyurina, Y. Y., Tyurin, V. A., Konduru, N. V., Potapovich, A. I., Osipov, A. N., Kisin, E. R., Schwegler‐Berry, D., Mercer, R. R., Castranova, V., et al. (2006) · Toxicology Letters · doi:10.1016/j.toxlet.2006.02.001 · Cited by 560 · see citing works
Highly efficient molecular delivery into mammalian cells using carbon nanotube spearing
Cai, D., Mataraza, J., Qin, Z., et al. (2005) · Nature Methods · doi:10.1038/nmeth761 · Cited by 552 · see citing works
Heller, D. A., Baik, S.-H., Eurell, T. E., & Strano, M. S. (2005) · Advanced Materials · doi:10.1002/adma.200500477 · Cited by 534 · see citing works
Mechanisms of chaperone-mediated autophagy
Majeski, A. E., & Dice, J. F. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.02.013 · Cited by 411 · see citing works
Polla, B. S., Kantengwa, S., François, D., Salvioli, S., Franceschi, C., Marsac, C., & Cossarizza, A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.13.6458 · Cited by 402 · see citing works
Liu, Y., Wu, D., Zhang, W., Jiang, X., He, C., Chung, T., Goh, S. H., & Leong, K. W. (2005) · Angewandte Chemie International Edition · doi:10.1002/anie.200500042 · Cited by 378 · see citing works
Sato, Y., Yokoyama, A., Shibata, K., Akimoto, Y., Ogino, S.-I., Nodasaka, Y., Kohgo, T., Tamura, K., Akasaka, T., Uo, M., et al. (2005) · Molecular BioSystems · doi:10.1039/b502429c · Cited by 351 · see citing works
Doh‐ura, K., Iwaki, T., & Caughey, B. W. (2000) · Journal of Virology · doi:10.1128/jvi.74.10.4894-4897.2000 · Cited by 323 · see citing works
Benzi, G., & Moretti, A. (1995) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(94)00244-e · Cited by 283 · see citing works
Nanoparticles as carriers for oral peptide absorption: Studies on particle uptake and fate
Florence, A. T., Hillery, A. M., Hussain, N., & Jani, P. U. (1995) · Journal of Controlled Release · doi:10.1016/0168-3659(95)00059-h · Cited by 260 · see citing works
Polyketal Nanoparticles: A New pH-Sensitive Biodegradable Drug Delivery Vehicle
Heffernan, M. J., & Murthy, N. (2005) · Bioconjugate Chemistry · doi:10.1021/bc050176w · Cited by 257 · see citing works
Bae, Y., Fukushima, S., Harada, A., & Kataoka, K. (2003) · Angewandte Chemie · doi:10.1002/ange.200250653 · Cited by 221 · see citing works
Lacerda, L., Soundararajan, A., Singh, R. N., et al. (2007) · Advanced Materials · doi:10.1002/adma.200702334 · Cited by 212 · see citing works
Nanoparticles and microparticles for drug and vaccine delivery.
Kreuter, J. (1996) · Europe PMC (PubMed Central) · Cited by 205 · see citing works
Immobilization of Heparin: Approaches and Applications
Linhardt, R. J., Murugesan, S., & Xie, J. (2008) · Current Topics in Medicinal Chemistry · doi:10.2174/156802608783378891 · Cited by 203 · see citing works
Carbon‐Nanotube Shape and Individualization Critical for Renal Excretion
Lacerda, L., Herrero, M. A., Venner, K., et al. (2008) · Small · doi:10.1002/smll.200800323 · Cited by 182 · see citing works
Carbon Nanotube Delivery of the GFP Gene into Mammalian Cells
Gao, L., Nie, L., Wang, T., et al. (2005) · ChemBioChem · doi:10.1002/cbic.200500227 · Cited by 180 · see citing works
Fullerene-based amino acid nanoparticle interactions with human epidermal keratinocytes
Rouse, J. G., Yang, J., Barron, A. R., & Monteiro-Riviere, N. A. (2006) · Toxicology in Vitro · doi:10.1016/j.tiv.2006.04.004 · Cited by 151 · see citing works
Pothakos, K., Kurz, M. J., & Lau, Y.-S. (2009) · BMC Neuroscience · doi:10.1186/1471-2202-10-6 · Cited by 134 · see citing works
Liang, Z., Liu, F., Grundke, I., Iqbal, K., & Gong, C. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04942.x · Cited by 134 · see citing works
Nanobiotechnology: Protein‐Nanomaterial Interactions
Kane, R. S., & Stroock, A. D. (2007) · Biotechnology Progress · doi:10.1021/bp060388n · Cited by 127 · see citing works
Comparative in vivo biocompatibility study of single- and multi-wall carbon nanotubes
Fraczek–Szczypta, A., Menaszek, E., Paluszkiewicz, C., et al. (2008) · Acta Biomaterialia · doi:10.1016/j.actbio.2008.05.018 · Cited by 126 · see citing works
Murr, L. E. (2008) · International Journal of Nanomedicine · doi:10.2147/ijn.s2464 · Cited by 102 · see citing works
Delayed oxidant‐induced cell death involves activation of phospholipase A2
Zhao, M., Brunk, U. T., & Eaton, J. W. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)03184-2 · Cited by 102 · see citing works
Use of Magnetic Nanoparticles to Visualize Threadlike Structures inside Lymphatic Vessels of Rats
Johng, H., Yoo, J. S., Yoon, T., et al. (2006) · Evidence-based Complementary and Alternative Medicine · doi:10.1093/ecam/nel057 · Cited by 94 · see citing works
Galantamine in Alzheimer’s disease
Razay, G., & Wilcock, G. K. (2007) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.8.1.9 · Cited by 89 · see citing works
Asumendi, A., Morales, M. C., Alvarez, A., et al. (2002) · British Journal of Cancer · doi:10.1038/sj.bjc.6600356 · Cited by 89 · see citing works
Acetylcholine esterase activity in mild cognitive impairment and Alzheimer’s disease
Herholz, K. (2008) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-007-0699-4 · Cited by 87 · see citing works
Interactions of single-wall carbon nanotubes with endothelial cells
Albini, A., Mussi, V., Parodi, A., Ventura, A., Principi, E., Tegami, S., Rocchia, M., Francheschi, E., Sogno, I., Cammarota, R., et al. (2009) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2009.08.001 · Cited by 73 · see citing works
Synthesis of carbon nanotube-supported Pt nanoparticles covered with silica layers
Takenaka, S., Arike, T., Nakagawa, K., et al. (2007) · Carbon · doi:10.1016/j.carbon.2007.11.011 · Cited by 72 · see citing works
Therapeutic potential of pyruvate therapy for mitochondrial diseases
Tanaka, M., Nishigaki, Y., Fuku, N., et al. (2007) · Mitochondrion · doi:10.1016/j.mito.2007.07.002 · Cited by 60 · see citing works
Lu, J. (2007) · Carbon · doi:10.1016/j.carbon.2007.04.013 · Cited by 59 · see citing works
Quantit Analysis: A Quantal Assay Refinement
Copenhaver, T. W., & Mielke, P. W. (1977) · Biometrics · doi:10.2307/2529311 · Cited by 55 · see citing works
Cytotoxic evaluation of injectable cyclodextrin nanoparticles
Bilensoy, E., Doğan, A. L., & Hıncal, A. A. (2006) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.58.5.0002 · Cited by 35 · see citing works
Dimitrova, D. S., & Getova-Spassova, D. P. (2006) · Journal of Pharmacological Sciences · doi:10.1254/jphs.fpe05006x · Cited by 34 · see citing works
Izquierdo, L. A., Barros, D. M., Medina, J. H., & Izquierdo, I. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(00)00286-2 · Cited by 32 · see citing works
Amatore, C. A., Arbault, S., Ferreira, D., et al. (2008) · Journal of Electroanalytical Chemistry · doi:10.1016/j.jelechem.2007.11.037 · Cited by 29 · see citing works
Mota, J. P. B., & Esteves, I. A. A. C. (2007) · Adsorption · doi:10.1007/s10450-007-9006-8 · Cited by 24 · see citing works
Studies on adsorption of phenol and substituted phenols on carbon nanotubes
Mao-gang, L. (2006) · Chemical Research and Application · Cited by 5 · see citing works
pH-sensitive polymers for cytoplasmic drug delivery
Varshosaz, J. (2008) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.18.8.959 · Cited by 2 · see citing works
[Effect of ionol on superoxide radical metabolism in murine liver].
Ls, V., & Sm, G. (1999) · PubMed · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs
Naqvi, S., Panghal, A., & Flora, S. J. S. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00494 · Cited by 305 · see citing works
Nanotechnology—novel therapeutics for CNS disorders
Srikanth, M., & Kessler, J. A. (2012) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.76 · Cited by 198 · see citing works
Therapeutics, imaging and toxicity of nanomaterials in the central nervous system.
Nunes, A., Al-Jamal, K. T., & Kostarelos, K. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.03.026 · Cited by 75 · see citing works
Functionalized Carbon Nanotubes: Revolution in Brain Delivery
Wang, J. T.-W., & Al-Jamal, K. T. (2015) · Nanomedicine · doi:10.2217/nnm.15.114 · Cited by 53 · see citing works
- Authors
- Yang, Z., Zhang, Y., Yang, Y., Sun, L., Han, D., Li, H., & Wang, C.
- Affiliations
- National Center for Nanoscience and Technology (CN)
- Corresponding author
- Zhang, Yingge
- Venue
- Nanomedicine Nanotechnology Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 6
- Issue
- 3
- Pages
- 427-441
- ISSN
- 1549-9634 (ISSN-L)
- OpenAlex
- W2145295565
- Cited by
- 311
- References
- 60
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 24 · 2023: 27 · 2022: 16 · 2021: 20 · 2020: 18 · 2019: 25 · 2018: 16 · 2017: 24 · 2016: 21 · 2015: 16 · 2014: 17 · 2013: 21 · 2012: 24
- FWCI
- 12.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nanomedicine Nanotechnology Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Graphene and Nanomaterials Applications
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- single-walled carbon nanotubes, lysosomes, mitochondria, mitochondrial toxicity, phosphatidylinositol 3-kinase, lysosomal-associated membrane protein 2, reactive oxygen species, mitochondrial membrane potential, Alzheimer's disease, drug carriers, nanoparticle toxicity, dose-dependent toxicity, brain drug delivery
- MeSH terms
- Acetylcholine, Alzheimer Disease, Animals, Autophagy, Brain, Cell Survival, Drug Carriers, Health Status, Intestinal Absorption, Lysosomes, Memory, Mitochondria, Organ Specificity, Spectrum Analysis, Raman, Subcellular Fractions, Reproducibility of Results, Nanotubes, Carbon, Nanomedicine, Mice
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
