Huang Yongkang, Chen Qixian, Lu Hongguang, An Jinxia, Zhu Huajie, Yan Xiangjie, Li Wei, Gao Hui
School of Chemistry and Chemical Engineering, Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, Tianjin University of Technology, Tianjin 300384, P. R. China.
J Mater Chem B. 2018 Nov 7;6(41):6660-6666. doi: 10.1039/c8tb02207k. Epub 2018 Oct 5.
Reversible stabilities are required for therapeutic (e.g. DNA) delivery systems to afford adequate stability in the journey to therapeutic targets but make the systems susceptible to structural disassembly and the liberation of their therapeutic payloads. For this purpose, we attempted to synthesize an oligo-ethyleneimine (OEI)-crosslinked polycation, characterized with self-sufficing reactive oxygen species (ROS) by virtue of a functional aggregation-induced emissive (AIE) component (with good near-infrared imaging functions) and an ROS-labile diselenide linkage. The strategic AIE component was capable of exerting facile ROS production upon convenient daylight irradiation (unprecedented ROS-producing efficiency of 80.14%), consequently helping to activate an endosomal escape functionality and the fragmentation of the OEI-crosslinked polycation into low molecular weight OEI products. Consequently, the engineered capabilities enabled the spatiotemporal control of the stabilities of the electrostatic-based DNA self-assembled formation so that it was adequately stable in the gene transportation journey to the targets but could reverse the stabilities to liberate pDNA to execute the subsequent biological processes, evidenced by the disassociation of the near-infrared emission of AIEgen and Cy5-pDNA. Therefore, our devised strategies provided tempting design implications for utilizing daylight as an impetus for the intracellular delivery of functional molecules, and thus could be developed further to find broad utilities in the transportation of a variety of biological substances in therapeutic applications.
治疗性(如DNA)递送系统需要可逆稳定性,以便在前往治疗靶点的过程中具有足够的稳定性,但又能使系统易于发生结构解体并释放其治疗载荷。为此,我们试图合成一种寡聚乙二胺(OEI)交联的聚阳离子,其通过功能性聚集诱导发光(AIE)组分(具有良好的近红外成像功能)和对活性氧(ROS)不稳定的二硒键来实现自足性ROS生成。这种策略性的AIE组分能够在方便的日光照射下轻松产生ROS(前所未有的80.14%的ROS产生效率),从而有助于激活内体逃逸功能,并使OEI交联的聚阳离子断裂成低分子量的OEI产物。因此,这些工程能力实现了对基于静电的DNA自组装形成稳定性的时空控制,使其在基因运输到靶点的过程中具有足够的稳定性,但又能逆转稳定性以释放pDNA来执行后续的生物过程,这由AIEgen和Cy5-pDNA的近红外发射解离所证明。因此,我们设计的策略为利用日光作为功能性分子细胞内递送的动力提供了诱人的设计思路,因此可以进一步开发,以在治疗应用中各种生物物质的运输中找到广泛的用途。