Harnessing the PEG-cleavable strategy to balance cytotoxicity, intracellular release and the therapeutic effect of dendrigraft poly-L-lysine for cancer gene therapy
作者： Min Tang , Haiqing Dong , Yongyong Li , Tianbin Ren
DOI: 10.1039/C5TB02224J
关键词:
摘要: Dendrimer catiomers like dendrigraft poly-L-lysine (DGL) have been very popular vectors for gene delivery recently; however, they generally suffer from serious cytotoxicity high density of positive charge. PEGylated DGL engineered using the PEG cleavable mechanism (DGL(R)-SS-mPEG) was first developed as a non-viral vector cancer intervention. Cleavable PEGylation catiomer in tumor relevant glutathione (GSH) conditions enables us to dramatically decrease well promote intracellular release and expression genetic payload. Like DGL, DGL(R)-SS-mPEG is capable efficiently complexing with plasmid DNA (pDNA) afford homogeneous compact nano-complexes. Those carrying nanostructures could be stably dispersed regular serum medium without GSH, but fast dis-assembly if subject 10 mM GSH. Compared non-cleavable counterpart, PEG-cleavable exhibited significantly higher enhanced green fluorescence protein (EGFP) against 293T cells. By small interfering RNA (siRNA-VEGF) therapeutic payload, complex nanoparticles demonstrated pronounced inhibition effect on cell growth vitro vivo. The promising results revealed universal strategy balance disadvantages advantages dendrimer future vector.
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