دورية أكاديمية
In situ triggering antitumor efficacy of alcohol-abuse drug disulfiram through Cu-based metal-organic framework nanoparticles
العنوان: | In situ triggering antitumor efficacy of alcohol-abuse drug disulfiram through Cu-based metal-organic framework nanoparticles |
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المؤلفون: | Lin Hou, Yanlong Liu, Wei Liu, Mervat Balash, Hongling Zhang, Yi Zhang, Huijuan Zhang, Zhenzhong Zhang |
المصدر: | Acta Pharmaceutica Sinica B, Vol 11, Iss 7, Pp 2016-2030 (2021) |
بيانات النشر: | Elsevier, 2021. |
سنة النشر: | 2021 |
المجموعة: | LCC:Therapeutics. Pharmacology |
مصطلحات موضوعية: | Disulfiram, Copper, Metal-organic framework, Hyaluronic acid, Lysosomal escape, DSF/Cu complex, Therapeutics. Pharmacology, RM1-950 |
الوصف: | Although approved as an alcohol-abuse drug, disulfiram (DSF) exhibited potential anticancer activity when chelated with copper (Cu). However, the low level of intrinsic Cu, toxicity originated from exogenous Cu supplementation, and poor stability of DSF in vivo severely limited its application in cancer treatment. Herein, we proposed an in situ DSF antitumor efficacy triggered system, taking advantages of Cu-based metal-organic framework (MOF). In detail, DSF was encapsulated into Cu-MOF nanoparticles (NPs) during its formation, and the obtained NPs were coated with hyaluronic acid to enhance the tumor targetability and biocompatibility. Notably, DSF loaded Cu-MOF NPs maintained stability and integrity without Cu2+ leakage in blood circulation, thus showing excellent biosafety. Once accumulating at tumor site, NPs were internalized into tumor cells via receptor-mediated endocytosis and released DSF and Cu2+ simultaneously in the hyaluronidase-enriched and acidic intracellular tumor microenvironment. This profile lead to in situ chelation reaction between DSF and Cu2+, generating toxic DSF/Cu complex against tumor cells. Both in vitro and in vivo results demonstrated the programmed degradation and recombination property of Cu-based MOF NPs, which facilitated the tumor-specific chemotherapeutic effects of DSF. This system provided a promising strategy for the application of DSF in tumor therapy. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2211-3835 |
Relation: | http://www.sciencedirect.com/science/article/pii/S2211383521000174; https://doaj.org/toc/2211-3835 |
DOI: | 10.1016/j.apsb.2021.01.013 |
URL الوصول: | https://doaj.org/article/6e2dfc5de8794eaa9967a10f80b9a0e8 |
رقم الأكسشن: | edsdoj.6e2dfc5de8794eaa9967a10f80b9a0e8 |
قاعدة البيانات: | Directory of Open Access Journals |
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