Nanoparticle-based delivery of harmine: A comprehensive study on synthesis, characterization, anticancer activity,...

The effective treatment of cancer presents numerous challenges, including drug resistance and the risk of detrimental effects on normal tissues. Harmine, a beta-carboline alkaloid, has demonstrated diverse biological properties. This study aimed to synthesize and characterize harmine encapsulated in polylactic-co-glycolic acid (PLGA) nanoparticles (Ha-PLGA-NPs) to investigate their potential as agents against cancer and angiogenesis. The synthesized Ha-PLGA-NPs were thoroughly characterized, exhibiting a connected rod-shaped crystal which some retaining the spherical shape of nanoparticles with an average size of 302.96 nm. Furthermore, the nanoparticles demonstrated a dispersion index of 0.23 and a surface charge of -16.51 mV. In vitro cytotoxicity assays conducted on the breast cancer cell line (MCF-7) revealed that Ha-PLGA-NPs possessed significant cytotoxic properties, with an observed IC₅₀ value of 87.74 μg/mL. Notably, no substantial cytotoxicity was observed in human foreskin fibroblasts, indicating a favorable selectivity towards cancer cells. Evaluation of the anti-angiogenic activity of Ha-PLGA-NPs demonstrated a concentration-dependent inhibition of angiogenesis. Mechanistic investigations indicated that the observed inhibition was mediated through the regulation of key genes involved in angiogenesis, including caspase 3, caspase 9, VEGF, and VEGF-R. In vivo studies involving dietary administration of Ha-PLGA-NPs in mice revealed improvements in weight gain, feed intake, liver enzyme levels, and redox potential. These findings underscore the potential of Ha-PLGA-NPs as a promising therapeutic agent for cancer treatment. The observed effects are attributed to their ability to induce programmed cell death and inhibit angiogenesis, thus offering a multifaceted approach to combat cancer.