Self-facilitated ROS-responsive nanoassembly of heterotypic dimer for synergistic chemo-photodynamic therapy
Self-facilitated ROS-responsive nanoassembly of heterotypic dimer for synergistic chemo-photodynamic therapy
复制标题
用于协同化学光动力疗法的自促进ROS响应异型二聚体纳米组装
DOI：
10.1016/j.jconrel.2019.04.001
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发表时间：
2019-05-28
影响因子：
10.8
通讯作者：
Sun, Jin
中科院分区：
文献类型：
--
作者：
Luo, Cong;Sun, Bingjun;Sun, Jin
针对临床肿瘤单药治疗效率低的问题，迫切需要开发有效的联合给药途径。然而，如何实现高效的同步共递送和协同治疗仍然是一个很大的挑战。在此，我们报道了一种用于多模式癌症治疗的异型化学光动力二聚体的自促进纳米组装。合理设计并合成了紫杉醇（PTX）和焦酚脲A （PPa）的活性氧响应二聚体。“二合一”二聚体作为载体材料和货物，可以在水中自组装成纳米颗粒，具有超高的共载能力和自促进的ros反应药物释放。肿瘤细胞中过量产生的内源性ROS与激光照射下ppa产生的ROS协同促进纳米组装体按需释放药物。活性氧引发纳米组装体的分解，有效地解决了光敏剂（PPa）的聚集猝灭（ACQ）效应难题。体外和体内实验结果表明，ptx启动的化疗联合ppa介导的PDT具有协同抗肿瘤活性。我们的研究结果为合理设计纳米载体以实现高效的协同肿瘤治疗提供了策略。
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.