Department of Chemistry , University of Texas at San Antonio , One UTSA Circle , San Antonio , Texas 78249 , United States.
College of Life Science and Chemistry, Jiangsu Key Laboratory of Biological Functional Molecules , Jiangsu Second Normal University , Nanjing , Jiangsu 210013 , PR China.
ACS Appl Mater Interfaces. 2018 Jul 25;10(29):24421-24430. doi: 10.1021/acsami.8b07124. Epub 2018 Jul 11.
Conjugated polymers can serve as good photosensitizers in biomedical applications. However, it remains unknown whether they are phototoxic to the supercoiled structure of DNA in improving gene delivery by the photochemical internalization (PCI) strategy, which complicates the application of conjugated polymers in gene delivery. In this work, we introduced a trace amount of cationic poly(phenylene ethynylene)s (cPPEs) into the polymeric shell of branched polyethylenimine (BPEI)/DNA complexes, studied the photosensitization of singlet oxygen by cPPEs, and confirmed that the supercoiled DNA is undamaged by the singlet oxygen generated by the photoexcitation of cPPEs. By taking advantage of the cPPE-mediated PCI effect, we report that the addition of the trace amount of cPPEs to the outer shell of the BPEI/DNA polyplexes could greatly amplify the transfection of gene green fluorescent protein on tumor cells with the efficiency from 14 to 86% without decreasing the cell viabilities, well solving the problem with a poor transfection capability of BPEI under low DNA-loading conditions. Our strategy to employ conjugated polymers as photosensitizing agents in gene delivery systems is simple, safe, efficient, and promising for broad applications in gene delivery areas.
共轭聚合物可用作生物医学应用中的良好光敏剂。然而，目前尚不清楚它们是否对 DNA 的超螺旋结构具有光毒性，从而改善光化学内化（PCI）策略下的基因传递，这使得共轭聚合物在基因传递中的应用变得复杂。在这项工作中，我们在支化聚乙烯亚胺（BPEI）/DNA 复合物的聚合物壳中引入了痕量的阳离子聚（苯乙炔）（cPPE），研究了 cPPE 对单线态氧的光敏化作用，并证实超螺旋 DNA 未被 cPPE 光激发产生的单线态氧破坏。利用 cPPE 介导的 PCI 效应，我们报告说，将痕量的 cPPE 添加到 BPEI/DNA 聚电解质复合物的外壳中，可以大大提高基因绿色荧光蛋白在肿瘤细胞中的转染效率，从 14%提高到 86%，而不会降低细胞活力，很好地解决了 BPEI 在低 DNA 载量条件下转染能力差的问题。我们在基因传递系统中使用共轭聚合物作为光敏剂的策略简单、安全、高效，有望在基因传递领域得到广泛应用。
