Synthesis, characterization, and evaluation of the cytotoxic effects of caffeine nanoparticles on K562 cancer cell line.

Caffeine (1, 3, 7-trimethylxanthine) can be used as an anti-cancer compound in low concentrations. Considering this potential and the advantages of nanotechnology, including targeted delivery and low doses of compounds, caffeine nanoparticles were produced using a spontaneous nanoemulsion production method. Nanoparticles with an average diameter of 168 ± 1.03 nm, a polydispersity index of 0.2, and desirable stability were produced. After treatment with free caffeine and caffeine nanoemulsion, the viability of K562 cancer cells was measured using the MTT test, which showed that free caffeine and caffeine nanoemulsion, after 48 h, killed 50% of cancer cells at a concentration of 555.23 ± 1.7 µg/ml and 285.71 ± 3 µg/ml, respectively. Evaluation of genes involved in the induction of apoptosis in cancer cells showed the prominent role of caspase-3 in the induction of apoptosis. Also, free caffeine and caffeine nanoemulsion increased the expression level of P53 by 2- and 4-fold compared to the control group, and the expression ratio of Bax/Bcl2 increased by 10- and 15-fold, respectively. The biocompatibility evaluation test results showed that the caffeine nanoemulsion in the concentrations used in this study had no cytotoxic effects on PMBC and RBC cells and could be used for therapeutic purposes. In general, the results of this study showed that caffeine nanoemulsions not only have more potent anti-cancer activity than free caffeine but also show minimal cytotoxicity and better biocompatibility than free caffeine on normal cells. Our findings show that caffeine nanoparticles are a potential candidate for cancer treatment use as a therapeutic agent.