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.
Yanfang Zhou,Bin Yang,Xianyue Ren,Zhenzhen Liu,Zheng Deng,Luming Chen,Yubin Deng,Li-Ming Zhang,Liqun Yang
A series of hyperbranched cationic amylopectin derivatives conjugated with 1,2-ethylenediamine, diethylenetriamine and 3-(dimethylamino)-1-propylamine residues, named as EDA-Amp, DETA-Amp and DMAPA-Amp, were synthesized by the N,N’- carbonyldiimidazole activation method at room temperature. Their structures were characterized by FTIR and 1 H NMR analyses, and their buffering capability was assessed by acid-base titration. The amylopectin derivatives exhibited better blood compatibility and lower cytotoxicity when compared to branched polyethyleneimine (bPEI) in the hemolysis and MTT assays . Atomic force microscopy and optical microscopy confirmed that the amylopectin derivatives exhibited lower damage for erythrocytes than bPEI. The amylopectin derivatives could bind and condense plasmid DNA (pDNA) to form the complexes with the size ranging from 100 to 300 nm. The resultant complexes showed higher transfection efficiency in 293T cells than in A549 cells. The DMAPA-Amp derivative-mediated gene transfection for Forkhead box O1 exhibited higher protein expression than that of the EDA-Amp and DETA-Amp derivatives in 293T cells, which was analyzed by western blot , flow cytometry and Hoechst staining assay. On the basis of these data, amylopectin derivatives exhibit potential as nonviral gene vectors .
危险品化学品经营许可证（带存储）