Targeted therapy for HCC using dumbbell-like nanoparticles conjugated to monoclonal antibodies against VEGF and cancer stem cell receptors in mice

Abstract

Abstract Background Hepatocellular carcinoma (HCC) is the leading cause of death worldwide. Nanoparticles allow early detection of tumor and delivery of chemotherapeutic drugs to the specific tumor site. This study aimed to assess the therapeutic role of dumbbell-like nanoparticles conjugated with monoclonal antibodies (mAbs) against both vascular endothelial growth factor (VEGF) and cluster of differentiation (CD) 90 (a cancer stem cell marker) in hepatocellular carcinoma experimental model. This study included 100 mice; HCC was induced chemically in 80 male Balb/c mice by diethylnitrosamine (DEN) and 20 mice served as normal control group. Mice were divided into four groups; pathological control group, mAbs-conjugated nanoparticles-treated group, nanoparticles (alone)-treated group and Avastin-treated group. Animals were sacrificed after one and two months of treatment for assessment of HCC response to treatment. Serum samples were collected and analyzed for alfa-feto protein (AFP), Caspase-3, VEGF-A by enzyme-linked immunosorbent assay (ELISA) technique and alanine transaminase (ALT) and aspartate transaminase (AST) by automated analyzer. Liver sections of sacrificed animals were stained with hematoxylin and eosin (H&E) for histopathological assessment. Results There were highly significant and significant differences (p value < 0.1 and < 0.5) between mAbs-conjugated nanoparticles-treated group and Avastin group, respectively, in comparison to pathological group. Both groups showed a significant decrease in all serum parameters, but mAbs-conjugated nanoparticles-treated group had more potent improvement effect when compared with Avastin group. MAbs-conjugated nanoparticles-treated group also showed the best improvement in liver architecture. Conclusion Dumbbell-like nanoparticles conjugated to anti-CD90 and Avastin is a novel therapeutic tool for HCC to target cancer stem cells and endothelial cells in the niche of the tumor.