Histidine-tagged dialdehyde cellulose nanoparticles to study the co-treatment effect of curcumin and 3-methyladenine on HepG2 cells

Abstract

The anticancer effects of curcumin (CUR) against hepatocellular carcinoma (HCC) cells have been well-documented. However, poor solubility limits its use in clinical practice. Natural delivery systems could help to overcome this restriction and reduce adverse effects on normal cells during cancer therapy. Besides, modification of carriers by amino acids can enhance their potential to enter and release payloads. For instance, histidine (His) not only induces pH responsivity but also protonated His inside the endosomes will possibly undergo endosomal bump and release of cargos in tumor cells. In addition, the small molecule 3-methyladenine (3-MA) has been reported to influence tumor control by altering autophagy in cells. This study intended to develop a pH-responsive nanocarrier based on dialdehyde cellulose (DAC) nanoparticles (NPs) to enhance the bioavailability and controlled release of CUR in HepG2 cells. Also, we add 3-MA to the culture media to evaluate their synergistic effect and autophagy inhibition. The physicochemical evaluations of NPs and the release kinetics studies showed proper fabrication as well as controlled and smart release of CUR from NPs. We found that combining CUR/DACHis with 3-MA could stimulate autophagy and had a synergistic effect on HepG2 cells (p < 0.05) while representing negligible toxic effects on normal fibroblasts.