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Issue 3, 2019
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A multifunctional polymeric gene delivery system for circumventing biological barriers

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

Graphical abstract: A multifunctional polymeric gene delivery system for circumventing biological barriers

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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, 2019,7, 384-392

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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, 2019, 7, 384
    DOI: 10.1039/C8TB03069C

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