TY - JOUR
T1 - Preparation of optimized lipid-coated calcium phosphate nanoparticles for enhanced in vitro gene delivery to breast cancer cells
AU - Tang, Jie
AU - Li, Li
AU - Howard, Christopher B.
AU - Mahler, Stephen M.
AU - Huang, Leaf
AU - Xu, Zhi Ping
N1 - Publisher Copyright:
© The Royal Society of Chemistry.
PY - 2015/7/29
Y1 - 2015/7/29
N2 - 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 cells in vitro, compared with the commercial transfection agent Oligofectamine™.
AB - 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 cells in vitro, compared with the commercial transfection agent Oligofectamine™.
UR - http://www.scopus.com/inward/record.url?scp=84939148053&partnerID=8YFLogxK
U2 - 10.1039/c5tb00912j
DO - 10.1039/c5tb00912j
M3 - Article
AN - SCOPUS:84939148053
SN - 2050-7518
VL - 3
SP - 6805
EP - 6812
JO - Journal of Materials Chemistry B
JF - Journal of Materials Chemistry B
IS - 33
ER -
