posted on 2021-10-14, 20:14authored byCuiping Jiang, Yuan Wang, Peiyi Liang, Yao Chen, Ziming Zhuang, Lu Zhang, Yankui Yi, Li Liu, Qiang Liu
Specific delivery of NCEH1 plasmid
is a promising approach to boost
the cholesterol removal from lipid-laden macrophages for antiatherosclerosis.
Polyethylenimine (PEI) is one of the most efficient gene carriers
among nonviral vectors. However, the high transfection activity of
PEI is always accompanied by profound cytotoxicity. To tackle the
paradox between transfection efficiency and safety, we constructed
a novel ATP-responsive multifunctional supramolecular polymer by cross-linking
functionalized low-molecular-weight PEI via a boronic ester bond for
NCEH1 plasmid delivery. The supramolecular polymer could condense
NCEH1 plasmids to form stable nanosized polyplexes when the w/w ratios
of the polymer and gene were higher than 2. ATP-triggered degradation
of the polymer and pDNA release were characterized by a series of
studies, including 1H NMR, 31P NMR, XPS, agarose
gel electrophoresis, and ethidium bromide exclusion tests. In addition,
the changes in particle size and morphology were observed in the presence
of ATP. Interestingly, the supramolecular polymer showed broad spectrum
antioxidant activities by measuring the elimination rates of different
reactive oxygen species. In addition, the supramolecular polymer displayed
a high buffering capability and good cytocompatibility as demonstrated
by the results of the buffering capacity, a hemolysis assay, and a
cytotoxicity test. Importantly, it was revealed that the supramolecular
polymer/NCEH1 plasmid polyplex formulated at a w/w ratio of 20 was
most effective in enhancing cholesterol removal from lipid-laden macrophages
and reducing the accumulation of lipid droplets as evidenced by transfection
study, cholesterol efflux assay, and oil red O staining studies. Collectively,
the ATP-responsive multifunctional supramolecular polymer holds great
potential for safe and efficient gene delivery for antiatherosclerosis.