Biocompatibility, Cytotoxicity, Antimicrobial and Epigenetic Effects of Novel Chitosan-Based Quercetin Nanohydrogel in Human Cancer Cells

Saber Abbaszadeh,1 Marzieh Rashidipour,2 Peyman Khosravi,1 Soroosh Shahryarhesami,3 Behnam Ashrafi,2 Mozhgan Kaviani,4 Mostafa Moradi Sarabi1,2,5,6 1Department of Biochemistry and Genetics, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran; 2Nutritional Health Research C...

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Autores principales: Abbaszadeh S, Rashidipour M, Khosravi P, Shahryarhesami S, Ashrafi B, Kaviani M, Moradi Sarabi M
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Lenguaje:EN
Publicado: Dove Medical Press 2020
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Acceso en línea:https://doaj.org/article/fddec17aafd34616ad39218e76be766f
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Sumario:Saber Abbaszadeh,1 Marzieh Rashidipour,2 Peyman Khosravi,1 Soroosh Shahryarhesami,3 Behnam Ashrafi,2 Mozhgan Kaviani,4 Mostafa Moradi Sarabi1,2,5,6 1Department of Biochemistry and Genetics, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran; 2Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran; 3Functional Genome Analysis/B070, German Cancer Research Center (DKFZ), Heidelberg, Germany; 4Department of Internal Medicine, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran; 5Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran; 6Hepatitis Research Center, Lorestan University of Medical Sciences, Khorramabad, IranCorrespondence: Mostafa Moradi SarabiDepartment of Biochemistry and Genetics, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, IranEmail sarabless2003@yahoo.comBackground: Previous studies have reported that quercetin (Q) has a potential antibacterial and anticancer activity. However, its application is limited by many important factors including high hydrophobicity and low absorption.Methodology: In the current study, we synthesized and characterized (Patent) a novel chitosan-based quercetin nanohydrogel (ChiNH/Q). Encapsulation efficiency was confirmed by UV/VIS spectrophotometer. Physicochemical characterization of ChiNH/Q was assessed by PDI, DLS, SEM, FTIR, and XRD. The toxicity of the ChiNH/Q against five strains of the pathogen and HepG2 cells was examined. Moreover, the quantification of ChiNH/Q on genomic global DNA methylation and expression of DNMTs (DNMT1/3A/3B) in HepG2 cancer cells were evaluated by ELISA and real-time PCR, respectively.Results: Under the SEM-based images, the hydrodynamic size of the ChiNH/Q was 743.6 nm. The changes in the PDI were 0.507, and zeta potential was obtained as 12.1 mV for ChiNH/Q. The FTIR peak of ChiNH/Q showed the peak at 627 cm− 1 corresponded to tensile vibrational of NH2-groups related to Q, and it is the indication of Q loading in the formulation. Moreover, XRD data have detected the encapsulation of ChiNH/Q. The ChiNH/Q showed a potent antimicrobial inhibitory effect and exerted cytotoxic effects against HepG2 cancer cells with IC50 values of 100 μg/mL. Moreover, our data have shown that ChiNH/Q effectively reduced (65%) the average expression level of all the three DNMTs (p< 0.05) and significantly increased (1.01%) the 5-methylated cytosine (5-mC) levels in HepG2 cells.Conclusion: Our results showed for the first time the bioavailability and potentiality of ChiNH/Q as a potent antimicrobial and anticancer agent against cancer cells. Our result provided evidence that ChiNH/Q could effectively reduce cellular DNMT expression levels and increase genomic global DNA methylation in HepG2 cancer cells. Our results suggest a potential clinical application of nanoparticles as antimicrobial and anticancer agents in combination cancer therapy.Keywords: chitosan nanohydrogel, quercetin, cytotoxic activity, antimicrobial activity, DNA methylation, gene expression