Evaluation of the Synergistic Cytotoxicity of Camptothecin with Silver Nanoparticles: Potential Anti-angiogenic, Anti-inflammatory, and Antioxidant Agents

Background:The high cytotoxicity of camptothecin is considered one of the greatest problems, aside from resistance within the course of cancer therapy.Conversely, silver nanoparticles (SNPs) provide great potential for increasing drug efficacy and reducing adverse effects.The purpose of the research was to explore the cytotoxic impact of camptothecin with SNPs on Various cancer cell lines and also to determine the level of several inflammatory, oxidative stress and angiogenesis biomarkers as possible targets influenced by these treatments.Methods: The SNPs were produced by Aspergillus flavus and characterization was performed by scanning electron microscopy (SEM) and zetasizer.SNPs were tested separately and in combination with camptothecin against normal fibroblast cells and different cancer cell lines including A549, HT-29 MCF7 and PANC-1.In addition, several inflammatory, oxidative stress and angiogenesis biochemical markers were evaluated using Enzyme Linked Immuno Assay (ELISA).Results: SNPs significantly increased the toxicity of camptothecin against A549, MCF7, and PANC-1 cells at 0.75 g/ml, while having insignificant toxicity on normal fibroblast cells.In addition, SNPs caused a decrease in vascular endothelial growth factor (VEGF) production and changed the inflammatory marker and antioxidant enzyme profile; thus, it was evident that co-incubation of SNPs and camptothecin effectively interrupted the pathways important for cancer cell survivability.Conclusion: Combined SNPs and camptothecin increase the potentiating effect of camptothecin cytotoxicity and affect several cancer-related processes such as oxidative stress, inflammation, and tumor vascularization.This approach offered a unique strategy against cancer treatment, particularly for cancers that do not respond to chemotherapeutic agents like pancreatic cancer.More research is required to establish this combination for its therapeutic application.