Pure redox-sensitive paclitaxel–maleimide prodrug nanoparticles: Endogenous albumin-induced size switching and improved antitumor efficiency
| العنوان: | Pure redox-sensitive paclitaxel–maleimide prodrug nanoparticles: Endogenous albumin-induced size switching and improved antitumor efficiency |
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| المؤلفون: | Zhonggui He, Dongchun Liu, Dong Zhang, Mengchi Sun, Hao Ling, Jin Sun, Xinyu Lou |
| المصدر: | Acta Pharmaceutica Sinica B, Vol 11, Iss 7, Pp 2048-2058 (2021) Acta Pharmaceutica Sinica. B |
| بيانات النشر: | Elsevier, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Maleimide, Paclitaxel, RM1-950, Conjugated system, Abraxane, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pharmacokinetics, General Pharmacology, Toxicology and Pharmaceutics, Cytotoxicity, 030304 developmental biology, 0303 health sciences, Breast cancer treatment, Disulfide bond, Albumin, Prodrug-based nano-drug delivery systems, Prodrug/albumin nanoaggregates, Prodrug, Redox-sensitive, chemistry, 030220 oncology & carcinogenesis, Cancer cell, Biophysics, Original Article, Therapeutics. Pharmacology |
| الوصف: | A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer. However, its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier. Herein, we report an albumin-bound tumor redox-responsive paclitaxel prodrugs nano-delivery strategy. Using diverse linkages (thioether bond and disulfide bond), paclitaxel (PTX) was conjugated with an albumin-binding maleimide (MAL) functional group. These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles (NPs) in aqueous solution without any excipients. By immediately binding to blood circulating albumin after intravenous administration, NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates in vivo, facilitating PTX prodrugs accumulation in the tumor region via albumin receptor-mediated active targeting. The tumor redox dual-responsive drug release property of prodrugs improves the selectivity of cytotoxicity between normal and cancer cells. Moreover, disulfide bond-containing prodrug/albumin nanoaggregates exhibit long circulation time and superior antitumor efficacy in vivo. This simple and facile strategy integrates the biomimetic characteristic of albumin, tumor redox-responsive on-demand drug release, and provides new opportunities for the development of the high-efficiency antitumor nanomedicines. Graphical abstract The paclitaxel–maleimide prodrugs nanoparticles integrate the biomimetic characteristic of albumin, tumor redox-responsive on-demand drug release and pave the way for designing targeted delivery nano-platform for tumor therapy.Image 1 |
| اللغة: | English |
| تدمد: | 2211-3835 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c0b26adc5428d5c466bc78cd49841d9b http://www.sciencedirect.com/science/article/pii/S2211383520308364 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c0b26adc5428d5c466bc78cd49841d9b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22113835 |
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