Self-facilitated ROS-responsive nanoassembly of heterotypic dimer for synergistic chemo-photodynamic therapy.

Autor: Luo C; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Sun B; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Wang C; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Zhang X; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Chen Y; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Chen Q; Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, PR China., Yu H; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Zhao H; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Sun M; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Li Z; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Zhang H; School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Kan Q; School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Wang Y; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., He Z; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Sun J; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China. Electronic address: sunjin@syphu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2019 May 28; Vol. 302, pp. 79-89. Date of Electronic Publication: 2019 Apr 01.
DOI: 10.1016/j.jconrel.2019.04.001
Abstrakt: There is an urgent need to develop efficient combination drug delivery approaches to address the low efficiency of clinical cancer monotherapy. However, how to achieve high-efficient synchronous co-delivery and synergistic therapy remains a big challenge. Herein, we report a self-facilitated nanoassembly of a heterotypic chemo-photodynamic dimer for multimodal cancer therapy. A reactive oxygen species (ROS)-responsive dimer of paclitaxel (PTX) and pyropheophorbide a (PPa) is rationally designed and synthesized. The "Two-in-One" dimer serves as both carrier material and cargo, could self-assemble into nanoparticles in water with ultrahigh co-loading capacity and self-facilitated ROS-responsive drug release. The endogenous ROS overproduced in tumor cells together with PPa-generated ROS under laser irradiation synergistically facilitate on-demand drug release from the nano-assembly. The disintegration of nanoassembly triggered by ROS effectively addresses the dilemma of aggregation-caused quenching (ACQ) effect of photosensitizer (PPa). Both in vitro and in vivo results suggest that PTX-initiated chemotherapy in combination with PPa-mediated PDT exhibits synergistic antitumor activity. Our findings provide a strategy for the rational design of nanocarrier for high-efficient synergetic cancer therapy.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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