| Autor: |
Sun, Bingjun, Chen, Yao, Yu, Han, Wang, Chen, Zhang, Xuanbo, Zhao, Hanqing, Chen, Qin, He, Zhonggui, Luo, Cong, Sun, Jin |
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| Zdroj: |
Acta Biomaterialia; Jul2019, Vol. 92, p219-228, 10p |
| Abstrakt: |
The combination of chemotherapy with photodynamic therapy (PDT) holds promising applications in cancer therapy. However, co-encapsulation of chemotherapeutic agents and photosensitizers (PS) into the conventional nanocarriers suffers from inefficient co-loading and aggregation-caused quenching (ACQ) effect of PS trapped in dense carrier materials. Herein, we report a light-activatable photodynamic PEG-coated prodrug nanoplatform for core–shell synergistic chemo-photodynamic therapy. A novel photodynamic polymer is rationally designed and synthesized by conjugating pyropheophorbide a (PPa) to polyethylene glycol 2000 (PEG 2k). PPa is used as the hydrophobic and photodynamic moiety of the amphipathic PPa-PEG 2k polymer. Then, a core–shell nanoassembly is prepared, with an inner core of a reactive oxygen species (ROS)-responsive oleate prodrug of paclitaxel (PTX) and an outer layer of PPa-PEG 2k. PPa-PEG 2k serves for both PEGylation and PDT. Instead of being trapped in the inner core, PPa in the outer PPa-PEG 2k layer significantly alleviates the ACQ effect. Under laser irradiation, ROS generated by PPa-PEG 2k not only is used for PDT but also synergistically promotes PTX release in combination with the endogenous ROS overproduced in tumor cells. The photodynamic PEG-coated nanoassemblies demonstrated synergistic antitumor activity in vivo. Such a unique nanoplatform, with an inner chemotherapeutic core and an outer photodynamic PEG shell, provides a new strategy for synergistic chemo-photodynamic therapy. The combination of chemotherapy with photodynamic therapy (PDT) holds promising prospects in cancer therapy. However, it remains a tremendous challenge to effectively co-deliver chemotherapeutic drugs and photosensitizers into tumors. Herein, we construct a photodynamic PEGylation-coated prodrug-nanoplatform for high-efficiency synergistic cancer therapy, which is composed of a light-activatable PPa-PEG 2k shell and a ROS-responsive paclitaxel (PTX) prodrug core. The PPa-PEG 2k -generated ROS not only was used for synergistic PTX release but also synergistically facilitated tumor cell apoptosis in combination with PTX-initiated chemo-cytotoxicity. The light-activatable nanoassemblies exhibited multiple drug delivery advantages including high co-loading efficiency, self-enhanced PTX release, extended circulation time, favorable biodistribution, and potent synergistic anticancer activity. Our findings provide a new strategy for the rational design of advanced nano-DDS for high-efficiency combinational chemo-photodynamic therapy. [ABSTRACT FROM AUTHOR] |
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