The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Enhanced Tumor-Specific Disulfiram Chemotherapy by In Situ Cu2+ Chelation-Initiated Nontoxicity-to-Toxicity Transition
Abstract
The antitumor activity of disulfiram (DSF), a traditional US Food and Drug Administration-approved drug for the treatment of “alcohol-dependence”, is Cu 2+ -dependent, but the intrinsic anfractuous biodistribution of copper in the human body and copper toxicity induced by exogenous copper supply have severely hindered its in vivo application. Herein, we report an in situ Cu 2+ chelation-enhanced DSF-based cancer chemotherapy technique, using a tumor-specific “nontoxicity-to-toxicity” transition strategy based on hollow mesoporous silica nanoparticles as the functional carrier. Cu 2+ -doped, DSF-loaded hollow mesoporous silica nanoparticles were constructed for the rapid release of Cu 2+ ions induced by the mild acidic conditions of the tumor microenvironment. This resulted in the rapid biodegradation of the nanoparticles and accelerated DSF release once the particles were endocytosed into tumor cells. The resulting in situ chelation reaction between the coreleased Cu 2+ ions and DSF generated toxic CuET products and concurrently, Fenton-like reactions between the generated Cu + ions and the high levels of H 2 O 2 resulted in the production of reactive oxygen species (ROS) in the acidic tumor microenvironment. Both in vitro cellular assays and in vivo tumor-xenograft experiments demonstrated the efficient Cu-enhanced and tumor-specific chemotherapeutic efficacy of DSF, with cocontributions from highly toxic CuET complexes and ROS generated within tumors. This work provides a conceptual advancement of nanoparticle-enabled “nontoxicity-to-toxicity” transformation in tumors, to achieving high chemotherapeutic efficacy and biosafety.
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Cites
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ROS-Generating Mitochondrial DNA Mutations Can Regulate Tumor Cell Metastasis
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Intracellular Glutathione Detection Using MnO2-Nanosheet-Modified Upconversion Nanoparticles
Deng, R., Xie, X., Vendrell, M., Chang, Y.-T., & Liu, X. (2011) · Journal of the American Chemical Society · doi:10.1021/ja2100774 · Cited by 936
Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4
Skrott, Z., Mistrik, M., Andersen, K. K., Friis, S., Majera, D., Gursky, J., Ozdian, T., Bartkova, J., Turi, Z., Moudry, P., et al. (2017) · Nature · doi:10.1038/nature25016 · Cited by 807
Nanoparticle-triggered in situ catalytic chemical reactions for tumour-specific therapy
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Self-citationOxygen Reduction by Homogeneous Molecular Catalysts and Electrocatalysts
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Cited by
Selective Targeting of Cancer Cells by Copper Ionophores: An Overview
Oliveri, V. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.841814 · Cited by 367
Wang, M., Chang, M., Chen, Q., Wang, D., Li, C., Hou, Z., Lin, J., Jin, D., & Xing, B. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120093 · Cited by 322
Biosafety of mesoporous silica nanoparticles; towards clinical translation
Lérida-Viso, A., Estepa-Fernández, A., García-Fernández, A., Martí-Centelles, V., & Martínez-Máñez, R. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.115049 · Cited by 279
Metallodrugs in cancer nanomedicine
Peña, Q., Wang, A., Zaremba, O., Shi, Y., Scheeren, H. W., Metselaar, J. M., Kiessling, F., Pallares, R. M., Wuttke, S., & Lammers, T. (2022) · Chemical Society Reviews · doi:10.1039/d1cs00468a · Cited by 259
The combination of disulfiram and copper for cancer treatment
Li, H., Wang, J., Wu, C., Wang, L., Chen, Z.-S., & Cui, W. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.04.003 · Cited by 185
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Metadata
- Authors
- Wu, W., Yu, L., Jiang, Q., Huo, M., Lin, H., Wang, L., Chen, Y., & Shi, J.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-06-28
- Volume
- 141
- Issue
- 29
- Pages
- 11531-11539
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2954483872
- Cited by
- 359
- References
- 37
- FWCI
- 10.55
- Type
- journal article
- Language
- en
- Open access
- closed
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- Wu, W., Yu, L., Jiang, Q., Huo, M., Lin, H., Wang, L., Chen, Y., & Shi, J. (2019). Enhanced Tumor-Specific Disulfiram Chemotherapy by In Situ Cu2+ Chelation-Initiated Nontoxicity-to-Toxicity Transition. Journal of the American Chemical Society. https://doi.org/10.1021/jacs.9b03503
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