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siRNA-loaded poly(histidine-arginine)6-modified chitosan nanoparticle with enhanced cell-penetrating and endosomal escape capacities for suppressing breast tumor metastasis

Authors Sun P, Huang W, Kang L, Jin M, Fan B, Jin H, Wang Q, Gao Z

Received 4 December 2016

Accepted for publication 1 February 2017

Published 19 April 2017 Volume 2017:12 Pages 3221—3234


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Linlin Sun

Ping Sun,1 Wei Huang,1 Lin Kang,1 Mingji Jin,1 Bo Fan,1 Hongyan Jin,2 Qi-Ming Wang,1 Zhonggao Gao1

1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2Yanbian University Hospital, Jilin, People’s Republic of China

Abstract: An ideal carrier that delivers small interfering RNA (siRNA) should be designed based on two criteria: cellular-mediated internalization and endosomal escape. Poly(histidine-arginine)6(H6R6) peptide was introduced into chitosan (CS) to create a new CS derivative for siRNA delivery, 6-polyarginine (R6) as cell-penetrating peptides facilitated nanoparticle cellular internalization has been proved in our previous research, and 6-polyhistidine (H6) mediated the nanoparticle endosome escape resulted in the siRNA rapid releasing into tumor cytoplasm. H6R6-modified CS nanoparticles showed higher transfection efficiency and better endosomal escape capacity compared to ungroomed CS nanoparticle in vitro. Noticeably, H6R6-modified CS nanoparticles effectively inhibited tumor cell growth and metastases in vivo and significantly improved survival ratio. Therefore, we concluded that H6R6-modified CS copolymer can act as an ideal carrier for siRNA delivery and as a promising candidate in breast cancer therapy.

Keywords: poly(histidine-arginine)6-peptide-modified chitosan nanoparticle, cell-penetrating peptides, endosome/lysosome escape, gene delivery, breast carcinoma

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