Tang Jie, Li Li, Howard Christopher B, Mahler Stephen M, Huang Leaf, Xu Zhi Ping
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia.
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.
J Mater Chem B. 2015 Sep 7;3(33):6805-6812. doi: 10.1039/C5TB00912J. Epub 2015 Jul 29.
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 , compared with the commercial transfection agent Oligofectamine.
脂质包被的磷酸钙（LCP）纳米颗粒（NPs）仍然是用于siRNA全身递送的一个有吸引力的选择。先前的研究表明，反应物的化学计量会影响纳米结构磷酸钙（CaP）颗粒的大小和形态。然而，尚不清楚诸如Ca/P摩尔比和混合方式等合成参数如何影响LCP NPs对siRNA的负载和保护，以及随后的siRNA递送效率。在本研究中，我们发现Ca/P摩尔比对于控制颗粒大小、zeta电位、分散状态、siRNA负载和保护至关重要。基于siRNA的负载效率和容量以及siRNA保护效果，我们提出了一种优化的LCP NPs递送系统。优化后的LCP NPs具有中空的球形结构，平均粒径约为40 nm，能够在含血清的培养基和PBS中保持其稳定性超过24 h，具有pH敏感的溶解特性。与市售转染试剂Oligofectamine相比，优化后的LCP NPs在维持封装的siRNA完整性和在培养基中的胶体稳定性方面具有卓越能力，使得该制剂能够实现siRNA在细胞内的积累增加以及对人乳腺癌细胞生长抑制作用增强。
