Bioinspired Synthesis of Large-Pore, Mesoporous Hydroxyapatite Nanocrystals for the Controlled Release of Large Pharmaceutics

Mesoporous hydroxyapatite (HA) rod-like nanocrystals (MHANs) with large and tunable mesopores and small particle sizes were synthesized using a novel bioinspired route where mesoporous silica nanoparticles (MSNs) acted as effective nucleating agents, and fetuin (an abundant serum protein) inhibited the growth of HA. Under the cooperative influences of the MSNs and fetuin, the nucleation and growth processes of MHANs were effectively controlled such that nanosized HA crystals with dumbbell morphologies, mesoporous structures, and large surface areas were produced. This synthetic strategy was also controllable such that MHANs with particle sizes of 235-515 nm, pore sizes of 21.1-30.5 nm, and surface areas of 130-225 m(2) g(-1) could be systematically produced by tuning the fetuin concentration. The MHANs were then investigated as drug delivery vehicles and exhibited a high loading capacity and sustained release of large pharmaceutics, as shown through a model large-molecule protein. Demonstration of effective intracellular uptake and low cytotoxicity confirmed the potential of the MHANs as carriers of large pharmaceutics.