Chen Tong, Gu Tongxu, Cheng Liang, Li Xiang, Han Gaorong, Liu Zhuang
State Key Laboratory of Silicon Materials, School of Materials Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, China.
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China.
Biomaterials. 2020 Oct;255:120202. doi: 10.1016/j.biomaterials.2020.120202. Epub 2020 Jun 13.
Overexpression of P-glycoprotein (P-gp), which is responsible for pumping chemotherapeutic drugs out of tumor cells, has been recognized as an important cause of drug resistance in conventional chemotherapy. Herein, porous platinum nanoparticles (pPt NPs) are developed to enable the combined electrodynamic therapy (EDT) with chemotherapy. With polyethylene glycol (PEG) coating, the obtained pPt-PEG NPs could be loaded with anticancer drug doxorubicin (DOX) by utilizing the porous structure of pPt NPs. Those pPt-PEG NPs are able to produce reactive oxygen species (ROS) by triggering water decomposition under electric field, independent of O and HO contents in the tumor. Furthermore, the ROS generated during EDT could induce the inhibition of P-glycoprotein (P-gp), in turn enhancing the efficacy of chemotherapeutic agents by facilitating intracellular accumulation of drugs. As the results, excellent synergetic therapeutic effects were observed by combining chemotherapy with EDT using DOX-loaded pPt (DOX@pPt-PEG) NPs, as demonstrated by both in vitro and in vivo experiments. This study demonstrates a new concept of combinational cancer therapy with superior therapeutic efficacy.
P-糖蛋白（P-gp）负责将化疗药物泵出肿瘤细胞，其过表达已被认为是传统化疗中耐药性的重要原因。在此，开发了多孔铂纳米颗粒（pPt NPs）以实现电动力疗法（EDT）与化疗的联合应用。通过聚乙二醇（PEG）包覆，利用pPt NPs的多孔结构，所制备的pPt-PEG NPs能够负载抗癌药物阿霉素（DOX）。这些pPt-PEG NPs能够通过在电场下引发水分解产生活性氧（ROS），而与肿瘤中的O₂和H₂O₂含量无关。此外，EDT过程中产生的ROS可诱导P-糖蛋白（P-gp）的抑制，进而通过促进药物在细胞内的积累增强化疗药物的疗效。结果，通过使用负载DOX的pPt（DOX@pPt-PEG）NPs将化疗与EDT联合应用，在体外和体内实验中均观察到了优异的协同治疗效果。本研究展示了一种具有卓越治疗效果的联合癌症治疗新概念。
