Calcium phosphate nanoparticles-based systems for siRNA delivery.

Xiaochun Xu,Xueqin Zhao,Lawrence Keen,Zehao Li,Xiangdong Kong

doi:10.1093/rb/rbw010

Abstract

Despite the enormous therapeutic potential of siRNA as a treatment strategy, the delivery is still a problem due to unfavorable biodistribution profiles and poor intracellular bioavailability. Calcium phosphate (CaP) co-precipitate has been used for nearly 40 years for in vitro transfection due to its non-toxic nature and simplicity of preparation. The surface charge of CaP will be tuned into positive by surface modification, which is important for siRNA loading and crossing cell membrane without enzymatic degradation. The new siRNA carrier system will also promote the siRNA escape from lysosome to achieve siRNA sustained delivery and high-efficiency silence. In this review, we focus on the current research activity in the development of CaP nanoparticles for siRNA delivery. These nanoparticles are mainly classified into lipid coated, polymer coated and various other types for discussion.

Highlights

SiRNA is a short dsRNA, which is known for its ability to silence gene expression in a sequence specific manner (RNA interference) [1, 2]. siRNA is produced when long double-stranded RNA precursors are cleaved by the endonuclease dicer into smaller molecules, and enter the RNA-induced silencing complex [3,4,5,6]
After further modifying lipid-coated calcium phosphate (LCP)-I with a PEG linker, they found that the LCP nanoparticles had excellent siRNA delivery activity in vitro and in a xenograft tumor model
A wide variety of Calcium phosphate (CaP) nanoparticles have been developed for efficient siRNA delivery by coating suitable PEG, liposome or other polymer to CaP crystals

Summary

Introduction

SiRNA (small interfering RNA) is a short dsRNA (typically 20– 27 bp), which is known for its ability to silence gene expression in a sequence specific manner (RNA interference) [1, 2]. siRNA is produced when long double-stranded RNA precursors are cleaved by the endonuclease dicer into smaller molecules, and enter the RNA-induced silencing complex [3,4,5,6]. Giger et al [50] used PEGylated chelating agents (PEG-alendronate and PEG-inositol-pentakisphosphate) to prepare CaP nanoparticles through co-precipitation and found that CaP had stable enough properties to efficiently deliver siRNA in vitro (Fig. 1)[]. Zhang et al [65] utilized electrostatic interactions between the anionic charges of siRNA and the cationic charges on the PEGylated CaP crystal surface to prepare CaP/siRNA nanoparticles with sizes between 90 and 200 nm, resulting in the nanoparticles showing significant gene silencing efficiency on cultured cells.

Results

Conclusion