X-ray-Triggered CO Release Based on GdW10/MnBr(CO)5 Nanomicelles for Synergistic Radiotherapy and Gas Therapy

Carbon monoxide (CO) therapy has become a hot topic in the field of gas therapy because of its application prospect in the treatment of various diseases. Due to the high affinity for human hemoglobin, the main challenge of CO-loaded nanomedicine is the lack of selectivity and toxicity in the delivery process. Although many commercial CO-releasing molecules (CORMs) have been widely developed because of their ability to deliver CO, CORMs still have some disadvantages, including difficult on-demand controlled CO release, poor solubility, and potential toxicity, which are limiting their further application. Herein, an X-ray-triggered CO-releasing nanomicelle system (GW/MnCO@PLGA) based on GdW₁₀ nanoparticles (NPs) (GW) and MnBr(CO)₅ (MnCO) encapsulating in the poly(lactic-co-glycolic acid) (PLGA) polymer was constructed for synergistic CO radiotherapy (RT). The production of strongly oxidative superoxide anion (O₂^-•) active species can lead to cell apoptosis under the X-ray sensitization of GW. Moreover, strongly oxidative O₂^-• radicals further oxidize and compete with the Mn center, resulting in the on-demand release of CO. The radio/gas therapy synergy to enhance the efficient tumor inhibition of the nanomicelles was investigated in vivo and in vitro. Therefore, the establishment of an X-ray-triggered controlled CO release system has great application potential for further synergistic RT CO therapy in deep tumor sites.