Anticancer efficacy of albumin nanoparticles co-loaded with silver nanoparticles and 5FU in animal model of colon cancer

Colorectal cancer (CRC) remains a major challenge to global health and chemotherapy, while effective, often suffers from non-specificity, limited efficacy and severe side effects. 5-Fluorouracil (5FU), a cornerstone of chemotherapy for colorectal cancer, has a short half-life and systemic toxicity. Targeted delivery systems are crucial to overcome these limitations. The aim of this study was to develop and evaluate albumin nanoparticles (ANPs) co-loaded with green-synthesized silver nanoparticles (AgNPs) and 5FU (Ag-5FU-ANPs) as a potential strategy to improve chemotherapeutic efficacy and reduce toxicity in the treatment of colorectal cancer. The AgNPs were synthesized from a green tea extract, characterized (UV-Vis, TEM/SEM, DLS) and showed a spherical morphology with an average size of 89.9 nm. Four nanoparticle formulations (ANP, Ag-ANP, 5FU-ANP, Ag-5FU-ANP) were prepared using a solvent displacement method. Characterization revealed successful encapsulation efficiency (EE) (%EE > 70-80% efficiency) and controlled release kinetics (according to the Higuchi model, > 90% release in 3 days). In vitro studies in normal human fibroblast cells (HFF) showed acceptable cytotoxicity for Ag-5FU-ANP compared to free agents, with minimal hemolysis. In a 21-day colon cancer model using Wistar rats with CT26-induced tumors, intravenous administration of Ag-5FU-ANP showed the most significant anticancer effect, reducing tumor size and tumor weight compared to other groups. Histopathological analysis confirmed increased apoptosis and decreased necrosis in the Ag-5FU-ANP group. However, while the combination therapies showed increased renal toxicity compared to ANP, Ag-5FU-ANP showed less severe hematological toxicity (anemia, leukocytosis) than 5FU monotherapy. The blood analysis confirmed these results. These results suggest that Ag-5FU-ANPs represent a promising dual drug delivery system for colorectal cancer, improving therapeutic outcomes through better localization of the drug and potential exploitation of the anti-cancer properties of AgNPs, while mitigating some systemic side effects associated with 5FU monotherapy through controlled release. Further optimization is required to balance efficacy and toxicity for potential clinical application.