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

Author:
Luo, Cong, Sun, Bingjun, Wang, Chen, Zhang, Xuanbo, Chen, Yao, Chen, Qin, Yu, Han, Zhao, Hanqing, Sun, Mengchi, Li, Zhenbao, Zhang, Haotian, Kan, Qiming, Wang, Yongjun, He, Zhonggui, Sun, Jin
Source:
Journal of controlled release 2019 v.302 pp. 79-89
ISSN:
0168-3659
Subject:
antineoplastic activity, drug therapy, irradiation, nanocarriers, nanoparticles, neoplasm cells, neoplasms, paclitaxel, photosensitizing agents, reactive oxygen species
Abstract:
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.
Agid:
6358512