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  • Title: Evaluation of Histidylated Arginine-Grafted Bioreducible Polymer To Enhance Transfection Efficiency for Use as a Gene Carrier.
    Author: Nam JP, Nam K, Nah JW, Kim SW.
    Journal: Mol Pharm; 2015 Jul 06; 12(7):2352-64. PubMed ID: 26029979.
    Abstract:
    To increase cellular uptake and endosomal escape efficiency, various methods have been studied to efficiently deliver plasmid DNA (pDNA) into the cell. Here, we designed a histidylated arginine-grafted bioreducible polymer (HABP) as a nonviral gene carrier using different ratios of histidine and arginine-grafted bioreducible poly(cystaminebis(acrylamide)-diaminohexane) (poly(CBA-DAH)), known as ABP, to increase cellular uptake and endosomal escape efficiency. HABPs consist of arginine (cell penetrating functionality), histidine (endosome buffering functionality), and a disulfide bond backbone (bioreducible functionality in cytoplasm). These components result in the following: (1) polyplexes are easily taken up by cells, (2) polyplexes can easily escape from the endosome into the cytosol, and (3) pDNA can dissociate from polyplexes in reducing environments such as the cytoplasm. HABPs showed increased buffering capacity over histidine-ungrafted ABP, and HABPs formed nanosized polyplexes with pDNA. These polyplexes were about 90 nm in size and had positive charges of about of 30-40 mV. HABPs/pDNA polyplexes showed enhanced transfection efficiency and no significant cytotoxicity in comparison with polyethylenimine 25 kDa (PEI 25k), histidine-ungrafted ABP, and Lipofectamine (commercial reagent) in human cervical carcinoma (HeLa), rat cardiomyocytes (H9C2), and colon carcinoma (CT26) cells.
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