Self-Assembled Redox Dual-Responsive Prodrug-Nanosystem Formed by Single Thioether-Bridged Paclitaxel-Fatty Acid Conjugate for Cancer Chemotherapy.

Autor:	Luo C; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China., Sun J; Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China., Liu D; Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China., Sun B; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China., Miao L; Division of Molecular Pharmaceutics and Center of Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States., Musetti S; Division of Molecular Pharmaceutics and Center of Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States., Li J; Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China., Han X; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China., Du Y; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China., Li L; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China., Huang L; Division of Molecular Pharmaceutics and Center of Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States., He Z; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University , Shenyang 110016, P. R. China.
Jazyk:	angličtina
Zdroj:	Nano letters [Nano Lett] 2016 Sep 14; Vol. 16 (9), pp. 5401-8. Date of Electronic Publication: 2016 Aug 08.
DOI:	10.1021/acs.nanolett.6b01632
Abstrakt:	Chemotherapeutic efficacy can be greatly improved by developing nanoparticulate drug delivery systems (nano-DDS) with high drug loading capacity and smart stimulus-triggered drug release in tumor cells. Herein, we report a novel redox dual-responsive prodrug-nanosystem self-assembled by hydrophobic small-molecule conjugates of paclitaxel (PTX) and oleic acid (OA). Thioether linked conjugates (PTX-S-OA) and dithioether inserted conjugates (PTX-2S-OA) are designed to respond to the redox-heterogeneity in tumor. Dithioether has been reported to show redox dual-responsiveness, but we find that PTX-S-OA exhibits superior redox sensitivity over PTX-2S-OA, achieving more rapid and selective release of free PTX from the prodrug nanoassemblies triggered by redox stimuli. PEGylated PTX-S-OA nanoassemblies, with impressively high drug loading (57.4%), exhibit potent antitumor activity in a human epidermoid carcinoma xenograft. This novel prodrug-nanosystem addresses concerns related to the low drug loading and inefficient drug release from hydrophobic prodrugs of PTX, and provides possibilities for the development of redox dual-sensitive conjugates or polymers for efficient anticancer drug delivery.
Databáze:	MEDLINE
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