Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, P. R. China.
Nanoscale. 2020 Apr 30;12(16):8890-8897. doi: 10.1039/d0nr00956c.
Selectively attenuating the protection offered by heat shock protein 90 (HSP90), which is indispensable for the stabilization of the essential regulators of cell survival and works as a cell guardian under oxidative stress conditions, is a potential approach to improve the efficiency of cancer therapy. Here, we designed a biodegradable nanoplatform (APCN/BP-FA) based on a Zr(iv)-based porphyrinic porous coordination network (PCN) and black phosphorus (BP) sheets for efficient photodynamic therapy (PDT) by enhancing the accumulation of the nanoplatforms in the tumor area and attenuating the protection of cancer cells. Owing to the favorable degradability of BP, the nanosystem exhibited accelerated the release of the HSP90 inhibitor tanespimycin (17-AAG) and an apparent promotion in the reactive oxygen species (ROS) yield of PCN as well as expedited the degradation of the PCN-laden BP nanoplatforms. Both in vitro and in vivo results revealed that the elevated amounts of ROS and reduced cytoprotection in tumor cells were caused by the nanoplatforms. This strategy may provide a promising method for attenuating cytoprotection to aid efficient photodynamic therapy.
选择性地削弱热休克蛋白 90（HSP90）的保护作用，HSP90 对于稳定细胞存活的基本调节剂至关重要，并在氧化应激条件下作为细胞保护者发挥作用，这是提高癌症治疗效率的一种潜在方法。在这里，我们设计了一种基于 Zr（iv）基卟啉多孔配位网络（PCN）和黑磷（BP）片的可生物降解纳米平台（APCN/BP-FA），通过增强纳米平台在肿瘤区域的积累并削弱癌细胞的保护作用，实现有效的光动力治疗（PDT）。由于 BP 的良好降解性，该纳米系统表现出加速 HSP90 抑制剂 17-AAG 的释放以及 PCN 的活性氧（ROS）产量的明显促进作用，并加速了负载 PCN 的 BP 纳米平台的降解。体外和体内结果均表明，ROS 的增加和肿瘤细胞中细胞保护作用的降低是由纳米平台引起的。这种策略可能为削弱细胞保护以辅助有效光动力治疗提供了一种有前途的方法。
