Treatment of cervical cancer by siRNA-loaded chitosan-coated calcium phosphate nanoparticles

doi:10.5246/jcps.2018.08.053

Abstract

Abstract:

In the present study, a chitosan-coated calcium phosphate nanoparticle (CS/CaP/siRNA NP) was developed to deliver siRNA for treatment of cervical cancer. The CS/CaP/siRNA NPs were prepared by the nano-precipitation method. The resulted NPs had a uniform spherical morphology with a size of ~194 nm and a zeta potential of ~+27 mV. In vitro experiments demonstrated that these NPs could efficiently deliver siEGFR into Hela cells and significantly down-regulate the EGFR expression level, which was probably associated with enhanced cell adhesion of chitosan, leading to extended residence time of cell internalization. Then the internalized CS/CaP/siRNA NPs exhibited pH-responsive disassembly of NPs, resulting in the enhanced release of siRNA and rapid lysosomal escape into cytoplasm. Moreover, in vivo anticancer results showed that the CS/CaP/siRNA NPs had significant inhibitory effects on tumor growth after intratumoral injection in Hela tumor xenografted nude mice, accompanying with no obvious changes of body weight during the whole experimental period. All these results indicated that the CS/CaP/siRNA NPs would have great potential to deliver siRNA for the treatment of cervical cancer via mucosal administration.

Key words: siRNA delivery, Chitosan, Calcium phosphate, pH-sensitive, Cervical cancer

CLC Number:

R944

Supporting:

Piaopiao Li, Yi Yan, Haitao Zhang, Ru Wang, Huhu Han, Jiancheng Wang. Treatment of cervical cancer by siRNA-loaded chitosan-coated calcium phosphate nanoparticles[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(8): 517-529.

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