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 O₂ and H₂O₂ 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）的过量表达是导致化疗药物从肿瘤细胞中泵出的原因，已被认为是常规化疗中耐药性的重要原因。在本文中，开发了多孔铂纳米颗粒（pPt NPs）以实现与化学疗法相结合的电动疗法（EDT）。通过聚乙二醇（PEG）涂层，可以利用pPt NPs的多孔结构为获得的pPt-PEG NP加载抗癌药阿霉素（DOX）。那些pPt-PEG NP能够通过触发电场下的水分解而产生活性氧（ROS），而与O ₂和H ₂ O ₂无关肿瘤中的含量。此外，在EDT期间产生的ROS可以诱导P-糖蛋白（P-gp）的抑制，进而通过促进药物在细胞内的积累而增强化学治疗剂的功效。结果，如体外和体内实验所证实的，通过使用载有DOX的pPt（DOX @ pPt-PEG）NP将化学疗法与EDT联合使用，观察到了优异的协同治疗效果。这项研究证明了具有优异治疗功效的联合癌症治疗的新概念。