Preparation of chitosan modified poly(lactic-co-glycolic acid) nanoparticles containing hawthorn proanthocyanidins: SCC25 cell cycle arrest, antiproliferation, and apoptosis studies

Abstract

The present study aims at the preparation of a chitosan-PLGA-based proanthocyanidin from hawthorn fruit loaded nano-system (CS-PLGA-PHL) and investigate its inhibitory effect on SCC-25 cells and the related mechanisms. Methods: CS-PLGA-PHL nanocomposites were constructed by emulsion-solvent evaporation. The effect of CS-PLGA-PHL on the proliferation of human normal squamous epithelial hNOK cells were detected. The antitumor activity of CS-PLGA-PHL on SCC-25 cells were studied by cytotoxicity test, cell cycle and apoptosis analysis. The apoptotic protein and gene expression in SCC-25 cells was detected by western blotting and q-PCR. Results: The particle size distribution of CS-PLGA-PHL was narrow with an average of 177.60±41.00 nm. CS-PLGA-PHL did not show significant cytotoxicity to hNOK cells (IC50 > 50 μg/mL), with strong cytotoxicity to SCC-25 cells (IC50 = 1.21 μg/mL), which could block the G0/G1 phase of SCC-25 cells and increase the distribution of G2/M phase. Meanwhile, the apoptosis induction of CS-PLGA-PHL was higher than that of free PHL and PLGA-PHL group (P <0.05). The cell cycle inhibition and apoptosis induction may be due to the up regulation of apoptosis-associated proteins and genes. Conclusion: CS-PLGA-PHL nanocomposites can inhibit the cell cycle and promote apoptosis of SCC-25 cells by up regulating the expression of apoptosis-associated proteins and genes, suggesting that it has potential as a chemotherapeutic drug for the treatment of oral squamous cell carcinoma.