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Towards water-soluble [60]fullerenes for the delivery of siRNA in a prostate cancer model.

ABSTRACT: This paper presents two water-soluble fullerene nanomaterials (HexakisaminoC₆₀ and monoglucosamineC₆₀, which is called here JK39) that were developed and synthesized as non-viral siRNA transfection nanosystems. The developed two-step Bingel-Hirsch reaction enables the chemical modification of the fullerene scaffold with the desired bioactive fragments such as D-glucosamine while keeping the crucial positive charged ethylenediamine based malonate. The ESI-MS and ¹³C-NMR analyses of JK39 confirmed its high T_h symmetry, while X-ray photoelectron spectroscopy revealed the presence of nitrogen and oxygen-containing C-O or C-N bonds. The efficiency of both fullerenes as siRNA vehicles was tested in vitro using the prostate cancer cell line DU145 expressing the GFP protein. The HexakisaminoC₆₀ fullerene was an efficient siRNA transfection agent, and decreased the GFP fluorescence signal significantly in the DU145 cells. Surprisingly, the glycofullerene JK39 was inactive in the transfection experiments, probably due to its high zeta potential and the formation of an extremely stable complex with siRNA.

SUBMITTER: Korzuch J

PROVIDER: S-EPMC8134426 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Towards water-soluble [60]fullerenes for the delivery of siRNA in a prostate cancer model.

Korzuch Julia J Rak Monika M Balin Katarzyna K Zubko Maciej M Głowacka Olga O Dulski Mateusz M Musioł Robert R Madeja Zbigniew Z Serda Maciej M

Scientific reports 20210519 1

This paper presents two water-soluble fullerene nanomaterials (HexakisaminoC60 and monoglucosamineC60, which is called here JK39) that were developed and synthesized as non-viral siRNA transfection nanosystems. The developed two-step Bingel-Hirsch reaction enables the chemical modification of the fullerene scaffold with the desired bioactive fragments such as D-glucosamine while keeping the crucial positive charged ethylenediamine based malonate. The ESI-MS and 13</sup ...[more]

PMID: 34012024

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Project description:Liver cirrhosis is an outcome of a wide range of liver chronic diseases. It is attributed to oxidative stress; therefore, antioxidant usage could be a promising treatment of that. So, exploring the impact of effective free radical scavenger pristine C60 fullerenes on liver fibrosis and cirrhosis and their ability to interact with main growth factor receptors involved in liver fibrogenesis was aimed to be discovered. We used N-diethylnitrosamine/carbon tetrachloride-induced simulations of rat liver fibrosis (10 weeks) and cirrhosis (15 weeks). Pristine C60 fullerene aqueous colloid solution (C60FAS) was injected daily at a dose of 0.25 mg/kg throughout the experiment. Liver morphology and functional and redox states were assessed. C60 fullerenes' ability to interact with epidermal, vasoendothelial, platelet-derived, and fibroblast growth factor receptors (EGFR, VEGFR, PDGFR, and FGFR, respectively) was estimated by computational modeling. We observed that C60FAS reduced the severity of fibrosis in fibrotic rats (0.75 vs. 3.0 points according to Ishak score), attenuated the hepatocyte injury, normalized elevated blood serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and mitigated oxidative stress manifestation in liver tissue restoring its redox balance. When applied to cirrhotic animals, C60FAS reduced connective tissue deposition as well (2.4 vs. 5.4 points according to Ishak score), diminished ALP and LDH (by 16% and 61%), and normalized conjugated and nonconjugated bilirubin, restoring the liver function. Altered liver lipid and protein peroxides and glutathione peroxidase activity were also leveled. Within a computer simulation, it was shown that C60 fullerenes can block hinge prohibiting ATP binding for EGFR and FGFR and thus blocking associated signal pathways. This ability in addition to their antioxidant properties may contribute to C60 fullerene's antifibrotic action. Thus, C60FAS may have a substantial therapeutic potential as an inhibitor of liver fibrosis and cirrhosis.

Dataset Information

Towards water-soluble [60]fullerenes for the delivery of siRNA in a prostate cancer model.

Publications

Towards water-soluble [60]fullerenes for the delivery of siRNA in a prostate cancer model.

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