The anti‐cancer effect of chitosan/resveratrol polymeric nanocomplex against triple‐negative breast cancer; an in vitro assessment
Azam Bozorgi, Zahra Ojaghi Haghighi, Mohammad Rasool Khazaei, Mohammad Rasool Khazaei, Maryam Bozorgi, Mozafar Khazaei, Mozafar Khazaei
Abstract
Herein, the authors synthesised chitosan nanoparticles (Cs NPs) as a resveratrol (RSV) carrier and evaluated their efficacy in stimulating apoptosis in MDA-MB 231 cells. Blank (Cs NPs) and RSV- Cs NPs (RSV-Cs NPs) were synthesised via ionic gelation and characterised by using fourier-transform infrared spectroscopy (FTIR), Scanning electron microscope, dynamic light scattering/Zeta potential and RSV release. MDA-MB 231 cells were treated with RSV, Cs NPs and RSV-Cs NPs (24, 48, and 72 h), followed by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Cell toxicity was evaluated using lactate dehydrogenase assay, and real-time polymerase chain reaction was performed to explore apoptosis induction. FTIR spectra confirmed the NPs via the formation of cross-linking bonds. Cs and RSV-Cs NPs sizes were about 75 and 198 nm with 14 and 24 mV zeta potentials. The RSV entrapment efficiency was 52.34 ± 0.16%, with an early rapid release followed by a sustained manner. Cs and RSV-Cs NPs inhibited cell proliferation at lower concentrations and IC50 values. RSV-Cs NPs had the most cytotoxic effect and stimulated intrinsic apoptotic pathway, indicated by increased Bcl-2-associated x (BAX), BAX/Bcl-2 ratio, P53 expressions, reduced Bcl-2 and upregulated caspases 3, 8 and 9. RSV-Cs NPs have a great potential to suppress invasive breast cancer cell proliferation by targeting mitochondrial metabolism and inducing the intrinsic apoptotic pathway.