Engineering porous vaterite CaCO₃ nanostructures via alcohol-surfactant coordination in co-precipitation: A facile route to tunable drug-carrier platforms.

Calcium carbonate (CaCO₃) is widely studied for drug delivery because of its excellent biocompatibility, low toxicity, and the high surface area and porosity of its vaterite phase, which enable efficient drug loading and cellular uptake. However, the intrinsic metastability of vaterite leads to its transformation into stable calcite, which limits its practical applications. In this study, porous vaterite CaCO₃ nanoparticles were synthesized through a facile co-precipitation process assisted by alcohols and surfactants, which regulate ion diffusion and control the crystallization pathway. The effects of the alcohol type and concentration, as well as the surfactant mixing ratio, were systematically investigated to optimize the particle size, morphology, and phase composition. The synergistic regulation of solvent polarity and surfactant balance enabled the formation of uniform vaterite nanoparticles (∼300 nm) with high porosity and specific surface area (89.3 m²/g). Ovalbumin-a model antigen-was adsorbed onto the porous nanoparticles with an efficiency of > 99.1%. Moreover, in vitro cytotoxicity and antigen-presentation assays demonstrated excellent biocompatibility (cell viability >90%) and enhanced IL-2 secretion (∼2200 pg/mL), indicating potent immunostimulatory capability. The findings demonstrate that the alcohol-surfactant-assisted co-precipitation strategy provides a simple yet effective route for the controlled synthesis of stable, porous vaterite CaCO₃ nanoparticles. These nanostructures exhibit considerable potential as biocompatible carriers for antigen delivery, drug loading, and other advanced biomedical applications.