Controlling the Size and Polymorphism of Calcium Carbonate Hybrid Particles Using Natural Biopolymers

Calcium carbonate (CaCO3) nanoparticles have diverse applications in biomedicine, including ultrasound imaging, biosensing, drug delivery, and theranostics. One of its crystal polymorphs, vaterite, exhibits many unique features, such as its high solubility, porosity, and spherical shape, which make it suitable for drug delivery; however, the instability of this polymorph makes the large-scale fabrication of these particles challenging. In this work, we utilized a fast precipitation technique to fabricate CaCO3 hybrid particles, with the biocompatible polymeric additives bovine serum albumin (BSA) and polydopamine (PDA), a polymer with unique optical properties. The results showed that BSA and PDA can be used together to produce hybrid particles with variable sizes and polymorph compositions, depending on the reaction or mixing time applied. We also demonstrated that, by controlling other fabrication process parameters, including the PDA polymerization time, addition order of the salts, and the pairing of the salts with the polymer additives, we could tune the physicochemical properties of the resulting CaCO3 hybrid particles. These findings are important in designing hybrid particle systems with tailored properties for specific applications, including contrast-enhanced ultrasound and photoacoustic imaging, drug delivery, photothermal therapy, and cancer theranostics.