(617a) Colloidal Strontium Doped Calcium Phosphate Nanocomposites for Gene Therapy

Razieh Khalifehzadeh, Hong Shen*

Department of Chemical Engineering, University of Washington, Box 351750, Seattle, WA 98195

Recent advancements in nano-biotechnology are gaining increasing attention toward the intracellular delivery of various therapeutic and diagnostic agents. Some biomolecules, such as nucleic acids (e.g., DNA or siRNA), are both charged and large molecules. It is difficult for them to cross the cell membrane and elicit their desired effects. Therefore, an appropriate delivery system is necessitated to assist their cellular uptake and trafficking. Calcium phosphate (CaP) minerals, similar to inorganic minerals of natural bone, are highly biocompatible and biodegradable. Their inherent properties such as pH-dependent solubility provide advantages in delivery and controlled release of bioactive agents at various cellular and intracellular environments. Strontium stimulates pre-osteoblast differentiation and formation of new bone. In this work, we developed a one-step method to prepare strontium-doped calcium phosphate (Sr-CaP) nanoparticles, using a mineralizing solution prepared based on the modified simulated body fluid (SBF). In order to absorb and preserve the DNA molecules, the mineralization was conducted at 37 °C and physiological pH. The size and morphological analysis by scanning electron microscopy have shown that the nanoparticles are spherical and mono-dispersed. Adjusting the strontium content enabled us to tune the physical and chemical properties of DNA-incorporated nanoparticles and mediate the gene transfer in human fetal osteoblastic cell line (hFOB1.19).