Role of Folate Functionalized Human Serum Albumin Nano-formulation for Bleomycin Delivery on Gene Expression in Gastric Cancer Cells

Nanoparticles (NPs) are considered an effective and accurate approach for targeted drug delivery. This research focuses on the modification of human serum albumin (HSA) using folic acid (FA) to enhance the targeted delivery of bleomycin (BLM) to gastric cancer cells. The structure and properties of FA-HSA-BLM formulated nanoparticles were effectively analyzed. The methods utilized included dynamic light scattering (DLS), scanning electron microscopy (SEM), atomic force microscopy (AFM), and ultraviolet-visible spectroscopy (UV-Vis). The rate of drug release was measured. The toxicity and viability percentages of various treatments, including BLM, FA-HSA, and FA-BLM-HAS, were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Molecular docking models were created to examine the interactions between the BLM drug and AKT1, Caspace3, NF1, and P21, aiming to identify potential binding sites. The results demonstrate that the drug release is pH-dependent, exhibits high loading efficiency, and possesses sustained release capabilities in this nano-formulation. The cytotoxic effects of FA-HSA-BLM nanoparticles on SNU-5 cell lines indicate extended anticancer activity. RT-PCR was employed to assess the expression levels of the Capase3, NF1, p21, and Akt1 genes in tumor cells. Expression levels of Caspase 3 and NF1 genes were elevated, while p21 and Akt1 gene expression levels were decreased. Tumor cells (SNU-5) and healthy cells (CCL-241) exhibit no response to bare FA-HSA nanoparticles. An analysis of the results confirmed that the formulated nanoparticles (FA-BLM-HAS) exhibit significant therapeutic activity against gastric cancer, as indicated by their cell toxicity profile and the induction of apoptosis.