DNA-Templated Strontium-Doped Calcium Phosphate Nanoparticles for Gene Delivery in Bone Cells

Calcium phosphates (CaPs), constituents of the inorganic phase of natural bone, are highly biocompatible and biodegradable. Strontium (Sr) regulates the formation and resorption of bone. Incorporation of Sr into CaPs may target genes of interest to bone cells while regulating their function. In this work, we developed a single-step synthesis method to prepare Sr-doped CaP nanoparticles (SrCaP-DNA NPs) by using DNA as a template for controlling the mineralization and the stability of the colloidal solution. The resulting nanoparticles were monodispersed with well-controlled size, morphology, and composition. By using this method, we were able to fabricate CaP NPs with varying contents of Sr²⁺. We demonstrated that the stability of CaP NPs in extracellular environments increased when Sr²⁺ partially replaced Ca²⁺ in CaP NPs. We showed that the cellular uptake of SrCaP-DNA NPs and the efficiency of gene transfer and alkaline phosphatase activity in human fetal osteoblastic cell line (hFOB1.19) were dependent on the content of Sr²⁺ in NPs. Together with other studies, our results suggest SrCaP-DNA NPs can be optimized for targeted gene transfer to regulate function of bone cells, enabling applications such as bone tissue engineering and treating bone diseases.