Additive application for modulating physicochemical properties and antitumor effects of CaCO3nanodelivery systems

Calcium carbonate (CaCO3) nanoparticles are highly regarded for their excellent biocompatibility and distinctive pH responsiveness, making them an ideal nanocarrier system for anti-tumor therapy. The incorporation of additives during the preparation of CaCO3can significantly influence its morphology, particle size, and tumor inhibitory effects, necessitating a systematic study of these impacts. This study utilized the gas diffusion method to prepare CaCO3nanoparticles, introducing various additives such as hyaluronic acid, polyacrylic acid, polyvinyl pyrrolidone, fucoidan, and polyethyleneimine. Different additives were found to have diverse effects on the morphology, particle size, zeta potential, and pH responsiveness of CaCO3. Methotrexate was employed as a model drug to evaluate the cytotoxicity of CaCO3nanoparticles with different additives. Among them, hyaluronic acid-modified CaCO3nanoparticles exhibited ideal morphology, particle size, significant pH responsiveness, and tumor-targeting capabilities. In vitroand in vivoexperiments demonstrated their remarkable antitumor effects.