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

Int J Nanomedicine. 2020 Aug 11:15:5963-5975. doi: 10.2147/IJN.S263013. eCollection 2020.

Abstract

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-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: DNA methylation; antimicrobial activity; chitosan nanohydrogel; cytotoxic activity; gene expression; quercetin.

MeSH terms

  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Chitosan / chemistry
  • DNA (Cytosine-5-)-Methyltransferase 1 / metabolism
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methyltransferase 3A
  • Epigenesis, Genetic / drug effects*
  • Hep G2 Cells
  • Humans
  • Hydrogels / administration & dosage
  • Hydrogels / chemistry*
  • Hydrophobic and Hydrophilic Interactions
  • Microbial Sensitivity Tests
  • Nanostructures / administration & dosage
  • Nanostructures / chemistry*
  • Quercetin / administration & dosage
  • Quercetin / chemistry
  • Quercetin / pharmacokinetics
  • Quercetin / pharmacology*
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction

Substances

  • Anti-Infective Agents
  • Antineoplastic Agents, Phytogenic
  • DNMT3A protein, human
  • Hydrogels
  • Chitosan
  • Quercetin
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • DNMT1 protein, human