title: Preparation of optimized lipid-coated calcium phosphate nanoparticles for enhanced in vitro gene delivery to breast cancer cells.
abstract: Lipid coated calcium phosphate (LCP) nanoparticles (NPs) remain an attractive option for siRNA systemic delivery. Previous research has shown that the stoichiometry of reactants affects the size and morphology of nanostructured calcium phosphate (CaP) particles. However, it is unclear how synthesis parameters such as the Ca/P molar ratio and mixing style influence the siRNA loading and protection by LCP NPs, and subsequent siRNA delivery efficiency. In this research, we found that the Ca/P molar ratio is critical in controlling the size, zeta potential, dispersion state, siRNA loading and protection. Based on the siRNA loading efficiency and capacity as well as siRNA protection effectiveness, we suggested an optimized LCP NPs delivery system. The optimized LCP NPs had a hollow, spherical structure with the average particle size of ~40 nm and were able to maintain their stability in serum containing media and PBS for over 24 h, with a pH-sensitive dissolution property. The superior ability of optimized LCP NPs to maintain the integrity of encapsulated siRNA and the colloidal stability in culture medium allow this formulation to achieve improved cellular accumulation of siRNA and enhanced growth inhibition of human breast cancer cellsin vitro, compared with the commercial transfection agent Oligofectamine™.
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Howard
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia; School of Chemical Engineering, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Mahler
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Leaf
authors.initials: L
authors.lastname: Huang
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Zhi Ping
authors.initials: ZP
authors.lastname: Xu
keywords: Calcium phosphate nanoparticle; Cellular uptake; Gene loading efficiency; Lipid bilayer coating; siRNA delivery