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A Multifunctional Polymeric Gene Delivery System for Circumventing Biological Barriers

A Multifunctional Polymeric Gene Delivery System for Circumventing Biological Barriers

Huajie Zhu, Jinxia An, Chengcai Pang, Shuai Chen, Wei Li, Jinbiao Liu, Qixian Chen, Hui Gao

J Mater Chem B. 2019 Jan 21;7(3):384-392.

PMID: 32254725

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	CAS Number	Price
AP1010840171	Acetylene-1,2-diyl bis(boronic acid pinacol ester)	1010840-17-1	Price
AP365564074	3,5-Dimethoxyphenylboronic acid pinacol ester	365564-07-4	Price
AP849062175	2,2′:5′,2″-Terthiophene-5-boronic acid pinacol ester	849062-17-5	Price
AP864754198	1-(Thiophen-2-ylmethyl)-1H-pyrazole-4-boronic acid pinacol ester	864754-19-8	Price
LS793407	3,5-dimethylpyridine-4-boronic acid pinacol ester		Price

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