Tetraphenylene (TPE), characterized as a lipophilic and aggregation-induced-emissive fluorophore, was used to incorporate into an electrostatic self-assembled polyethylenimine-poly(ethylene glycol) (PEI–PEG)/plasmid DNA (pDNA) complexed micelle. The hydrophobic character of TPE appeared to drive a higher degree of condensation of the pDNA payload, which consequently resulted in not only strengthened colloidal stability of the constructed polyplex micelle but also improved biocompatibility by virtue of the elevated PEG crowdedness owing to the TPE-induced collapse of pDNA. These beneficial consequences potentially permitted a larger number of polyplex micelles to be internalized into the cells. PEG segments were designed to enable selective detachment from polyplex micelles in acidic milieu, e.g., the tumor microenvironment, and intracellular endosome compartment, based on the strategic arrangement of acid-responsive cleavable linkage between PEG and PEI. Upon PEG detachment, the exposure of cationic PEI/TPE polyplex was allowed to directly interact with the cell membrane, endosome membrane, and charged intracellular species, thus promoting cell internalization, endosome escape, and the release of the pDNA payload. Of note, this association of cationic PEI/TPE polyplex with the endosomal membrane could be further facilitated with the aid of lipophilic TPE, thereby eliciting pronounced destabilization potency to the endosome membrane and exerting an endosomal escape function. Eventually, the proposed system of these facile strategies, including responsive PEG detachment and functional TPE incorporation, was proven to provide efficient gene expression in the targeted tumors with an appreciable safety profile via systemic administration.

中文翻译：

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具有pH响应PEG分离和功能性四亚苯基掺入以促进系统性基因表达的多重胶束

四苯（TPE）具有亲脂性和聚集诱导发射荧光团的特征，被用于将静电自组装的聚乙烯亚胺-聚（乙二醇）（PEI-PEG）/质粒DNA（pDNA）复合胶束掺入。TPE的疏水性似乎促使pDNA有效负载发生更高程度的缩合，因此，不仅由于TPE引起的塌缩导致PEG拥挤而提高了构建的复合胶束的胶体稳定性，而且还改善了生物相容性。 pDNA。这些有益的结果潜在地允许大量的多聚体胶束被内化到细胞中。PEG片段经设计可从酸性环境（例如肿瘤微环境）中的多聚体胶束中选择性分离。和胞内内体区室，基于PEG和PEI之间酸响应性可裂解键的战略安排。PEG脱离后，允许阳离子PEI / TPE复合物的暴露直接与细胞膜，内体膜和带电的细胞内物质相互作用，从而促进细胞内化，内体逃逸和pDNA有效负载的释放。值得注意的是，借助亲脂性TPE可进一步促进阳离子PEI / TPE多聚体与内体膜的这种缔合，从而引起内体膜明显的去稳定能力并发挥内体逃逸功能。最终，这些灵活策略的拟议系统（包括响应性PEG脱离和功能性TPE掺入）