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

Background: 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 corresponded to tensile vibrational of NH-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 IC 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.