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Stabilized calcium phosphate hybrid nanocomposite using a benzoxaborole-containing polymer for pH-responsive siRNA delivery

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Abstract

Calcium phosphate (CaP) nanoparticles present a class of promising nonviral gene delivery carriers due to their easy-preparation procedure, low toxicity and high transfection efficiency. PEGylated polyanion block copolymer was widely used to control the CaP crystal growth during CaP co-precipitation with therapeutic genes. However, there also exists a competition between the entrapped gene and polyanion in the system, which results in reduced stability and low gene entrapment efficiency. To solve this problem, herein, we demonstrate a non-anion stabilization strategy using a boroxole-containing block polymer, PEG-b-poly(benzoxaborole) (PEG-PBO), which forms pH-responsive boronic ester bonds with ribose rings of siRNA and also excellently adhers to the hydroxyapatite surface of CaP. The PEG-PBO/siRNA/CaP nanocomposites exhibited high siRNA loading efficiency, low cell cytotoxicity and excellent colloidal stability at neutral pH. The nanocomposites easily entered cancer cells mainly via clathrin-mediated endocytosis and transferred into acidic lysosomes, where the boronic esters broke, nanoparticles dissociated, and siRNA released and escaped from lysosomes. PEG-PBO/siRNA/CaP nanocomposites showed significantly higher gene silencing efficacy than lipofectamine 2000/siRNA lipoplex in multiple cancer cells. Thus, PEG-PBO/siRNA/CaP nanocomposites possess potential for safe and effective siRNA delivery.

Graphical abstract: Stabilized calcium phosphate hybrid nanocomposite using a benzoxaborole-containing polymer for pH-responsive siRNA delivery

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Publication details

The article was received on 25 May 2018, accepted on 02 Oct 2018 and first published on 03 Oct 2018


Article type: Paper
DOI: 10.1039/C8BM00575C
Citation: Biomater. Sci., 2018, Advance Article
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    Stabilized calcium phosphate hybrid nanocomposite using a benzoxaborole-containing polymer for pH-responsive siRNA delivery

    Q. Zhou, Y. Wang, J. Xiang, Y. Piao, Z. Zhou, J. Tang, X. Liu and Y. Shen, Biomater. Sci., 2018, Advance Article , DOI: 10.1039/C8BM00575C

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