Chitosan modified by γ-ray-induced grafting of poly(tributyl-(4-vinylbenzyl)phosphonium) as a biosafe and high-efficiency gene carrier. (4th May 2017)

• Record Type: Journal Article
• Authors: Zeng, Kun; Lin, Fu-xing; Xie, Juan; Wang, Mo-zhen; Rong, Jie-lin; Zhao, Yu; You, Ye-zi; Asif, Anila; Ge, Xue-wu
• Is Part Of: New journal of chemistry. Volume 41:Number 10(2017)
• Page Start: 4182
• Page End: 4189
• Publication Date: 2017-05-04
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/c7nj00008a
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : Chitosan modified by γ-ray-induced grafting polymerization of tributyl-(4-vinylbenzyl)phosphonium chloride can be used as a safe and high-efficiency gene carrier. Abstract : The development of gene carriers with high delivery efficiency and enough biosafety to replace the current viral vectors and cationic liposomes has long been a key project to achieve the practical application of gene therapy. As an abundant natural polymer, chitosan (CS) possesses incomparably high biocompatibility. However, when it is used as a gene carrier, the gene transfection efficiency is rather disappointing. Herein, we prepared a novel chitosan derivative, poly(tributyl-(4-vinylbenzyl)phosphonium)-grafted CS (CS-P), via γ-ray radiation-induced grafting copolymerization of tributyl-(4-vinylbenzyl)phosphonium in an acidic solution of CS. The CS-P could combine with p EGFP through a complex coacervation method to form p EGFP-loaded CS-P complex particles with a size of about 150 nm and a high positive zeta potential of 41.7 ± 6.1 mV. Agarose gel electrophoresis and an MTT assay show that the p EGFP-loaded CS-P particles have excellent biosafety, superior to p EGFP-loaded unmodified CS particles. In vitro and in vivo gene transfection experiments based on HeLa cells confirmed that p EGFP loaded into CS-P particles exhibits much higher gene transfection efficiency than that loaded into unmodified CS. This work provides not only a new way to modify CS with quaternary phosphonium, but also a useful and feasible way to obtain new CS-based gene vectors with high gene transfection efficiency and biosafety for potentially practical clinic applications.