A dual-drug delivery hydrogel platform based on hollow calcium carbonate nanoparticles for enhanced multimodal tumor...

Multimodal cancer therapies that integrate gas and photodynamic approaches hold significant promise but are often limited by low drug loading rates, short treatment durations, and suboptimal overall therapeutic efficacy. In this study, we developed hollow calcium carbonate nanoparticles via a one-pot gas-diffusion approach, employing rational selection and concentration tuning of amino acid additives to regulate particle formation. Notably, by utilizing L-arginine as a regulating agent, we produced nanoparticles with a significant specific surface area of 197.96 m²/g. Subsequent PEGylated/liposomal surface modification endowed the nanoparticles with excellent biocompatibility and an impressive drug loading capacity of up to 28.8 % and 26.9 % for the nitric oxide donor L-arginine and the photosensitizer indocyanine green (ICG), respectively. The resulting drug-loaded hollow amorphous calcium carbonate nanoparticles (PCAI NPs) have shown effective synergistic treatment against tumors through multimodal therapy methods, including photodynamic therapy, nitric oxide gas therapy, photothermal therapy, and calcium overload-induced cytotoxicity. Furthermore, PCAI NPs were encapsulated in an injectable thermo-responsive hydrogel system composed of Pluronic F-127 and hyaluronic acid, creating a nano drug delivery system that enables sustained, prolonged, and localized drug release. This work presents a high-loading, multifunctional nanoplatform for enhanced and prolonged multimodal cancer therapy.