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

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Mansour W.; EL Fedawy S.F.; Atta S.A.; Zarie R.M.; Fouad N.T.A.; Maher S.; Hussein T.M.; Abdel Aziz D.M.; Kamel M.

Journal: Cancer Nanotechnology

Publisher: BioMed Central Ltd

Publication Date: 25 February 2023

Volume / Issue: Volume 14 / Issue 1

Article No.: 14

ISSN: 18686958

DOI: 10.1186/s12645-023-00163-0

Scopus: View on Scopus

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Mansour W., Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt; EL Fedawy S.F., Faculty of Medicine, Ain Shams University, Cairo, Egypt; Atta S.A., Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt; Zarie R.M., Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt; Fouad N.T.A., Faculty of Medicine, Ain Shams University, Cairo, Egypt; Maher S., Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt; Hussein T.M., Physiology Department, National Organization for Drug Control and Research Pyramids Branch, Giza, Egypt; Abdel Aziz D.M., Faculty of Medicine, Ain Shams University, Cairo, Egypt; Kamel M., Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt

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. © 2023, The Author(s).

Keywords

Avastin; CD90; Hepatocellular carcinoma; Nanoparticles; alanine aminotransferase; antibody conjugate; aspartate aminotransferase; bevacizumab; caspase 3; cell marker; cell receptor; diethylnitrosamine; gold nanoparticle; magnetite nanoparticle; monoclonal antibody; nanoparticle; Thy 1 membrane glycoprotein; vasculotropin; vasculotropin A; animal cell; animal experiment; animal model; animal tissue; Article; cancer stem cell; cause of death; controlled study; drug release; early cancer diagnosis; enzyme linked immunosorbent assay; female; histopathology; in vitro study; liver cell carcinoma; male; mitosis; molecularly targeted therapy; mouse; nonhuman; pH; spectroscopy; transmission electron microscopy

Citation Information

Scopus Citations: 6

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