Cellular uptake mechanism and comparative in vitro cytotoxicity studies of monomeric LMWP-siRNA conjugate
Journal of Industrial and Engineering Chemistry(2018)
摘要
The covalent attachment of CPPs to siRNA molecules offers great potential for CPP-mediated siRNA delivery. We recently reported a concise and high-yield synthesis strategy of the cell-permeable, cytosol-dissociable LMWP-siRNA covalent conjugate. Herein, cell uptake mechanism and cellular toxicity studies of this conjugate were performed to evaluate the potential of LMWP-siRNA conjugate for clinical translation. Cellular uptake mechanism study indicated that the conjugate could be taken up by cells via multiple pathways, including direct penetration of the plasma membrane and clathrin- and caveolae-independent endocytosis. In vitro cytotoxicity study revealed that the conjugation promoted internalization in a low-toxic fashion.
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关键词
Cell penetrating peptide,siRNA delivery,Covalent CPP-siRNA chemical conjugate,Cell uptake mechanism,Cytotoxicity
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