1 research outputs found
Evaluation of Histidylated Arginine-Grafted Bioreducible Polymer To Enhance Transfection Efficiency for Use as a Gene Carrier
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