Biomolecule-assisted green synthesis of nanostructured calcium phosphates and their biomedical applications

Calcium phosphates (CaPs) are ubiquitous in nature and vertebrate bones and teeth, and have high biocompatibility and promising applications in various biomedical fields. Nanostructured calcium phosphates (NCaPs) are recognized as promising nanocarriers for drug/gene/protein delivery owing to their high specific surface area, pH-responsive degradability, high drug/gene/protein loading capacity and sustained release performance. In order to control the structure and surface properties of NCaPs, various biomolecules with high biocompatibility such as nucleic acids, proteins, peptides, liposomes and phosphorus-containing biomolecules are used in the synthesis of NCaPs. Moreover, biomolecules play important roles in the synthesis processes, resulting in the formation of various NCaPs with different sizes and morphologies. At room temperature, biomolecules can play the following roles: (1) acting as a biocompatible organic phase to form biomolecule/CaP hybrid nanostructured materials; (2) serving as a biotemplate for the biomimetic mineralization of NCaPs; (3) acting as a biocompatible modifier to coat the surface of NCaPs, preventing their aggregation and increasing their colloidal stability. Under heating conditions, biomolecules can (1) control the crystallization process of NCaPs by forming biomolecule/CaP nanocomposites before heating; (2) prevent the rapid and disordered growth of NCaPs by chelating with Ca2+ ions to form precursors; (3) provide the phosphorus source for the controlled synthesis of NCaPs by using phosphorus-containing biomolecules. This review focuses on the important roles of biomolecules in the synthesis of NCaPs, which are expected to guide the design and controlled synthesis of NCaPs. Moreover, we will also summarize the biomedical applications of NCaPs in nanomedicine and tissue engineering, and discuss their current research trends and future prospects.