Nano-Encapsulated Coumarin Derivative, CS-QM2 Inhibits Neoplasm Growth: Experimented in Zebrafish Model

Abstract

Cancer remains a significant global health challenge with limited therapeutic success, prompting the need for innovative treatment strategies. This study investigates the anticancer potential of nano-encapsulated metal derivatives (CS-QM2) using a zebrafish model with chemically induced cellular neoplasia. Characterization of CS-QM2 nanoparticles revealed successful synthesis with a high entrapment efficiency and enhanced drug release under acidic conditions. Zebrafish embryos exposed to 7,12-Dimethylbenz[a]anthracene (DMBA) exhibited significant malformations, macrophage accumulation, and abnormal tissue growth, which were markedly reduced by CS-QM2 treatment. CS-QM2 significantly increases intracellular ROS, resulting in higher LPO and induces apoptosis in neoplasm tissues. Furthermore, CS-QM2 treatment alters the tumor microenvironment, reducing macrophage accumulation by decreasing neutral lipid droplets, disrupting TAM metabolic support and limiting their protumorigenic activities. Biochemical assays demonstrated restored activities of antioxidant enzymes SOD, CAT, and GSH. Gene expression analysis showed upregulation of apoptosis and tumor suppressor genes (cas3, p53) and downregulation of inflammatory genes (cox-2, nf-kb). Histological assessment and SEM analysis confirmed reduced neoplasm occurrence and tissue abnormalities. These findings suggest that CS-QM2 nanoparticles effectively inhibit neoplasm growth and modulate the tumor microenvironment through oxidative stress induction and gene expression regulation.