Cancer cell membrane camouflaged metal-organic framework for enhanced multi-model therapies of prostate tumor via cisplatin prodrug delivery

Cisplatin as a first-line drug showed some significant limitations in clinical use owing to seriously systemic toxicity, and acquired drug-resistance. Herein, we utilized PC-3 cell membrane camouflaged Mn-doped metal-organic framework to deliver low toxic tetravalent cisplatin prodrug (mMOF-Pt) for synergistic chemodynamic therapy (CDT) and chemotherapy of prostate tumor. Owing to homologous targeting action, the mMOF-Pt actively recognized prostate tumor. Upon special tumor microenvironment, the mMOF-Pt released ciplatin prodrug. Next, the tetravalent cisplatin prodrug could be reduced into high toxic cisplatin by over-expressed GSH, effective killing tumor cells. Meanwhile, the MOF catalyzed endogenous H 2 O 2 into highly toxic ·OH via Fenton-like reaction, which induced intracellular ROS production and significantly elevated oxidative stress level. Strong oxidative stress dramatically enhanced the sensitivity of tumor cells to chemotherapeutic drug, further amplifying the toxicity of cisplatin to tumor cells. In vivo experiment results demonstrated that the mMOF-Pt effectively accumulated in tumor site and significantly inhibited the growth of prostate tumor within low systemic toxicity. Moreover, the mMOF-Pt could be completely excreted out from body, which avoided potential risk for body. Overall, we considered that this work provided a great strategy for improving therapy of prostate cancer.