10.1021/acs.molpharmaceut.5b00013.s001
Joung-Pyo Nam
Joung-Pyo
Nam
Kihoon Nam
Kihoon
Nam
Jae-Woon Nah
Jae-Woon
Nah
Sung Wan Kim
Sung Wan
Kim
Evaluation of Histidylated Arginine-Grafted Bioreducible
Polymer To Enhance Transfection Efficiency for Use as a Gene Carrier
American Chemical Society
2015
Enhance Transfection Efficiency
disulfide bond backbone
bioreducible functionality
plasmid DNA
components result
nanosized polyplexes
colon carcinoma
nonviral gene carrier
H 9C
polyethylenimine 25 kDa
HABP
transfection efficiency
CT
buffering capacity
pDNA
Gene CarrierTo increase
ABP
90 nm
PEI
2015-07-06 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Evaluation_of_Histidylated_Arginine_Grafted_Bioreducible_Polymer_To_Enhance_Transfection_Efficiency_for_Use_as_a_Gene_Carrier/2152834
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.