A Novel H2O2 Generator for Tumor Chemotherapy-Enhanced CO Gas Therapy.

Keli Zhong,Dazhen Jiang,Ning Zeng,Zeming Liu,Weng Zeng,Yiping Wu,Ziqi Wang,Chunping Liu,Yang Li

doi:10.3389/fonc.2021.738567

Abstract

Carbon monoxide (CO) gas therapy is a promising cancer treatment. However, gas delivery to the tumor site remains problematic. Proper tunable control of CO release in tumors is crucial to increasing the efficiency of CO treatment and reducing the risk of CO poisoning. To overcome such challenges, we designed ZCM, a novel stable nanotechnology delivery system comprising manganese carbonyl (MnCO) combined with anticancer drug camptothecin (CPT) loaded onto a zeolitic imidazole framework-8 (ZIF-8). After intravenous injection, ZCM gradually accumulates in cancerous tissues, decomposing in the acidic tumor microenvironment, releasing CPT and MnCO. CPT acts as a chemotherapy agent destroying tumors and producing copious H2O2. MnCO can react with the H2O2 to generate CO, powerfully damaging the tumor. Both in vitro and in vivo experiments indicate that the ZCM system is both safe and has excellent tumor inhibition properties. ZCM is a novel system for CO controlled release, with significant potential to improve future cancer therapy.

Highlights

The targeted development of cancer treatment technology—including chemotherapy, radiotherapy, and immunotherapy—has enormous potential in tumor treatment, most such technologies are yet to be used routinely in the clinic [1,2,3,4,5]
The absorption of CPT, zeolitic imidazole framework-8 (ZIF-8), manganese carbonyl (MnCO), and ZCM was measured using UV–vis absorption spectroscopy, with results indicating the successful preparation of ZCM (Figure 1E)
The release rate of Carbon monoxide (CO) rapidly enhances with increasing H2O2 concentrations. This indicated that ZCM can release CO in response to the tumor microenvironment. This indicates that ZCM can help control payload release in the tumor environment, which is expected to alter the tumor microenvironment and realize CO gas therapy

Summary

A Novel H2O2 Generator for Tumor Chemotherapy-Enhanced

Reviewed by: Wei Wei, Memorial Sloan Kettering Cancer Center, United States Ting Zhuang, Xinxiang Medical University, China Jia Huang, Central South University, China. Proper tunable control of CO release in tumors is crucial to increasing the efficiency of CO treatment and reducing the risk of CO poisoning. To overcome such challenges, we designed ZCM, a novel stable nanotechnology delivery system comprising manganese carbonyl (MnCO) combined with anticancer drug camptothecin (CPT) loaded onto a zeolitic imidazole framework-8 (ZIF-8). MnCO can react with the H2O2 to generate CO, powerfully damaging the tumor Both in vitro and in vivo experiments indicate that the ZCM system is both safe and has excellent tumor inhibition properties. ZCM is a novel system for CO controlled release, with significant potential to improve future cancer therapy

INTRODUCTION

RESULTS AND DISCUSSION

CONCLUSION

ETHICS STATEMENT