Synthesis of Calcium Bisphosphonate/Calcium Polyacrylate Spheres for Gene Delivery.

Calcium bisphosphonate/calcium polyacrylate spheres were synthesized by a facile method and applied for the first time as gene vectors for transfection. The colloidal spheres of the PAA-Ca-HO complex, formed by sodium polyacrylate and calcium ions in the solution, were used as template to synthesize a spherical PAA-Ca-BPMP composite (CaBPMP/CaPAA) in the presence of 1,4-bis(phosphomethyl)piperazine (BPMP). The CaBPMP/CaPAA composite exhibits uniform and well-dispersed spheres with a particle size of about 200 nm as expected. The cytotoxicity assays confirm that CaBPMP/CaPAA spheres are quite safe for different cells even at a high concentration of 500 μg/mL. In vitro transfection results show that CaBPMP/CaPAA spheres serving as gene vectors are capable of transferring exogenous genes into different cells with about 25% of transfection efficiency and good reproducibility. The transfection capacity of CaBPMP/CaPAA spheres may be attributed to the controllable sphere morphology, low cytotoxicity, moderate DNA loading capacity, and bioresorbable property. The application of calcium phosphonates with adjustable surface properties derived from the different organic groups of phosphonic acid in gene delivery provides a new design idea for gene vectors.