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A Multifunctional Polymeric Gene Delivery System for Circumventing Biological Barriers

Abstract

Aiming to circumvent the pre-defined obstacles in the journey of gene transportation, we attempt to compile a number of functional components into tandem tri-copolymeric material. Herein, β-cyclodextrin-functionalized poly(glycerol methacrylate) (PG) segment and quaternary amine-functionalized poly[(2-acryloyl)-ethyl-(p-boronic acid pinacol ester benzyl)diethylammonium bromide] (BP) segment are schemed to complex DNA to formulate nanoscaled delivery system based on electrostatic interactions. The formulated polyplex is strengthened by the hydrophobic poly[2-(5,5-dimethyl-1,3-dioxan-2-yloxy)ethyl acrylate] (PDM) segment, affording improved complex stability. To retrieve the polyplex from the entrapment from acidic and digestive endo/lysosomes, light-stimulated ROS-producing 4,4'-(1,2-diphenylethene-1,2-diyl)bis(1,4-phenylene)diboronic acid (TPE) is installed in the cavities of cyclodextrin. Upon light irradiation, TPE is determined to produce abundant ROS, not only committing disruption of endo/lysosome membrane for polyplex escape from the entrapment but also inducing the transformation of the positive-charged BP to be negative charge. This charge conversion behavior, together with transformation of PDM to be hydrophilic responsive to acidic endosome pH gradient (pH 5.0), is envisioned to induce the dissociation of the electrostatically-assembled polyplex, thereby facilitating the release of DNA payload for the subsequent transcription machinery. This strategically-tailored and easily synthesized tandem tri-copolymer exhibit excellent gene expression activity and provide facile response to endogenous and exogenous stimuli for active gene expression.

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Publication details

The article was received on 21 Nov 2018, accepted on 07 Dec 2018 and first published on 07 Dec 2018


Article type: Paper
DOI: 10.1039/C8TB03069C
Citation: J. Mater. Chem. B, 2018, Accepted Manuscript
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    A Multifunctional Polymeric Gene Delivery System for Circumventing Biological Barriers

    H. Zhu, J. An, C. Pang, S. Chen, W. Li, J. Liu, Q. Chen and H. Gao, J. Mater. Chem. B, 2018, Accepted Manuscript , DOI: 10.1039/C8TB03069C

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