GOx-Functionalized Platelet Membranes-Camouflaging Nanoreactors for Enhanced Multimodal Tumor Treatment

Ying Du,1,2 Shujun Wang,3 Jianfeng Luan,3 Meilin Zhang,1,2 Baoan Chen,1,2,* Yanfei Shen2,* 1Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Blood Transfusion, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baoan Chen, Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China, Email cba8888@hotmail.com Yanfei Shen, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China, Email Yanfei.Shen@seu.edu.cnBackground: Glucose oxidase (GOx)-based starvation therapy is a new cancer treatment strategy. However, the characteristics such as limited curative effect and hypoxic tumor environment hinder its further application seriously.Methods: Herein, doxorubicin (DOX) loaded in hollow mesoporous copper sulfide (HMCuS) nanoparticles assembled with manganese dioxide (HMMD) as nanoshell was prepared. We developed a targeted enhanced cancer treatment method to camouflage HMMD by GOx-functionalized platelet (PLT) membranes (HMMD@PG).Results: GOx can be specially transported to the tumor site with PLT membrane for effective starvation treatment. Glucose and oxygen (O2) in the tumor were converted to H2O2 under the catalysis of GOx. HMMD can catalyze H2O2 to produce O2 and consume glutathione (GSH) in time, which regulates the tumor microenvironment (TME) and improves the adverse conditions of anti-tumor. In addition, DOX encapsulated in HMCuS-MnO2 release was accelerated from the nanoparticles after the “gatekeeper” MnO2 is consumed. The study of anti-tumor mechanism shows that the remarkable tumor suppressive ability of HMMD@PG comes from the three peaks synergy of starvation treatment, photothermal treatment (PTT), and chemotherapy. This nanoplatform disguised by PLT membrane has significant tumor inhibition ability, good biocompatibility and almost has no side effects in main organs.Conclusion: This work broadens the application mode of GOx and shows the new development of a multi-mode collaborative processing system of nanoplatforms based on cell membrane camouflage.Keywords: glucose oxidase, PLT membrane, nanoparticles, tumor microenvironment, tumor treatment