A pH-responsive and nitric oxide-producing nanocarrier for targeted therapy of melanoma

In this study, we developed and characterized L-A@HMSN-Pt@MPN, a pH-responsive controlled-release nanocarrier for targeted nitric oxide (NO) delivery to cancer cells. Leveraging the abundant hydrogen peroxide (H 2 O 2 ) within tumor cells, platinum nanoparticles (Pt NPs) catalytically generated oxygen (O 2 ), facilitating the conversion of L-arginine (L-Arg) to NO. The metal-phenol network (MPN) acted as a pH-responsive switch, controlling L-Arg release from hollow mesoporous silica nanospheres (HMSNs). We characterized the structural and functional properties of the nanocarrier, evaluated the NO generation capacity, and assessed its effects on cancer cells in vitro and in vivo . Results demonstrated that L-A@HMSN-Pt@MPN exhibited significant tumor-selective cytotoxicity with minimal impact on normal cells. Critically, it induced cancer cell apoptosis through NO and reactive oxygen species (ROS) production. In vivo studies confirmed its therapeutic efficacy and revealed no significant biosafety concerns. This study proposes a strategy for NO delivery, potentially facilitating further research in gas-mediated cancer therapy.