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

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
Journal of controlled release 2019 v.302 pp. 79-89
antineoplastic activity, drug therapy, irradiation, nanocarriers, nanoparticles, neoplasm cells, neoplasms, paclitaxel, photosensitizing agents, reactive oxygen species
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.