Delivery of Manganese Carbonyl to the Tumor Microenvironment using Tumor-Derived Exosomes for Cancer Gas Therapy and Low Dose Radiotherapy

Abstract The development of novel radiosensitizer with high selectivity and controllability is highly desirable. CO gas could cause damage to mitochondria and thus enhance RT effect. Controlled delivery of CO in tumor is important both to achieve high-efficiency of CO gas therapy and to decrease the risk of CO poisoning. In this study, manganese carbonyl (MnCO) loaded exosome nano-vesicles (MMV) to overcome this conundrum for tumor therapy is developed. After administration, MMV showed its admirable performance in active tumor-targeting, mitochondria damage and radiosensitization therapy. These MMV nanoparticles were able to facilitate robust CO evolution and consequent ROS generation in response to X-ray irradiation both in vitro and in vivo. Significantly, MMV could facilitate a 90% inhibition effect of tumor growth under very low dose (only 2Gy) RT, which is better than high dose (6Gy) radiotherapy. Overall, this study highlights a novel and practical approach to enhancing the efficacy of tumor RT, underscoring the value of future research in the field of CO medicine.