Preparation of optimized lipid-coated calcium phosphate nanoparticles for enhanced in vitro gene delivery to breast cancer cells

Tang, Jie, Li, Li, Howard, Christopher B., Mahler, Stephen M., Huang, Leaf and Xu, Zhi Ping (2015) Preparation of optimized lipid-coated calcium phosphate nanoparticles for enhanced in vitro gene delivery to breast cancer cells. Journal of Materials Chemistry B, 3 33: 6805-6812. doi:10.1039/c5tb00912j


Author Tang, Jie
Li, Li
Howard, Christopher B.
Mahler, Stephen M.
Huang, Leaf
Xu, Zhi Ping
Title Preparation of optimized lipid-coated calcium phosphate nanoparticles for enhanced in vitro gene delivery to breast cancer cells
Journal name Journal of Materials Chemistry B   Check publisher's open access policy
ISSN 2050-750X
2050-7518
Publication date 2015-07-29
Year available 2015
Sub-type Article (original research)
DOI 10.1039/c5tb00912j
Open Access Status Not Open Access
Volume 3
Issue 33
Start page 6805
End page 6812
Total pages 8
Place of publication Cambridge, United Kingdom
Publisher Royal Society of Chemistry
Language eng
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 similar to 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 (TM).
Formatted 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 cells in vitro, compared with the commercial transfection agent OligofectamineTM.
Keyword In vitro
Breast cancer
Optimized lipid-coated calcium phosphate nanoparticles
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID FT120100813
DP120104792
CA151652
Institutional Status UQ

 
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