期刊
JOURNAL OF CONTROLLED RELEASE
卷 302, 期 -, 页码 79-89出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2019.04.001
关键词
Nanoassembly; Heterotypic dimer; Self-facilitated; ROS-responsive; Chemo-photodynamic therapy
资金
- National Basic Research Program of China (973 Program) [2015CB932100]
- National Natural Science Foundation of China [81703451]
- China Postdoctoral Science Foundation [2017M611269, 2018T110233]
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.
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