Therapeutic potential of miRNA-26a-encapsulated nanoparticles against hepatocellular carcinoma in a murine model

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Hassan M.; Fernández-Piñeiro I.; Badiola I.; Elzallat M.; Sánchez A.; Aboushousha T.; Hafiz E.; El-Ahwany E.

Journal: Liver Research

Publisher: KeAi Communications Co.

Publication Date: December 2025

Volume / Issue: Volume 9 / Issue 4

Pages: 338–350

ISSN: 20962878

DOI: 10.1016/j.livres.2025.10.002

Scopus: View on Scopus

Document Type: Article

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

Authors and Affiliations

Hassan M., Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt; Fernández-Piñeiro I., Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain; Badiola I., Department of Cell Biology and Histology, Faculty of Medicine and Nursery, University of Basque Country, UPV/EHU, Leioa, Spain, Nanokide Therapeutics SL, Zitek Ed, Rectorado Bajo, B° Sarriena sn, Leioa, Spain; Elzallat M., Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt; Sánchez A., Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain, Genetics and Biology of the Development of Kidney Diseases Unit, Sanitary Research Institute (IDIS) of the University Hospital Complex of Santiago de Compostela, Santiago de Compostela, Spain; Aboushousha T., Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt; Hafiz E., Electron Microscopy Department, Theodor Bilharz Research Institute, Giza, Egypt; El-Ahwany E., Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt

Abstract

Background and aims Hepatocellular carcinoma (HCC) treatment options are limited due to the lack of effective curative therapies, and conventional chemotherapy has often demonstrated limited effectiveness and may be associated with significant toxicity. Therefore, innovative therapeutics for HCC are urgently needed. Here, we aimed to evaluate the effectiveness of microRNA (miRNA)-26a-encapsulated nanoparticles in HCC treatment. Methods Span-Oleylamine-chondroitin sulfate were prepared and eighty male BALB/c mice were divided into four groups: (i) negative control group (saline injection), (ii) HCC group (intraperitoneal injection of diethylnitrosamine (DEN), at 50 mg/kg/week for 18 weeks), (iii) miRNA-26a-treated HCC group (intrahepatical injection of 100 nmol free miRNA-26a once weekly for four weeks), and (iv) miRNA-26a-loaded nanoparticles-treated HCC group (intrahepatic injection of miRNA-26a-loaded nanoparticles once weekly for 4 weeks, starting from Week 14 of DEN induction). Then, all mice were subjected to biochemical, genetic, histopathological, and immunohistochemical examinations. Results The HCC group showed elevated serum levels of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-alpha), along with upregulated hepatic expression of P70S6K , transforming growth factor-beta , DNA methyltransferase 3 beta ( DNMT3b ), and Caspase-3 genes, as well as HepPar 1, Ki67, cyclin D1, and arginase 1 proteins (all P < 0.001). miRNA-26a treatment attenuated these changes; moreover, the miRNA-26a-encapsulated nanoparticles caused a more dramatic decrease of these markers, resulting in almost complete restoration of the normal hepatic architecture. Conclusions Administration of miRNA-26a-encapsulated nanoparticles induced nearly total regression of HCC, suppression of cancer cell growth and angiogenesis, and induction of tumor necrosis. This study demonstrates the therapeutic efficacy of restoring the imbalanced expression of miRNA in the liver. Therefore, the clinical translation of this miRNA-based strategy warrants further investigation. © 2025 The Third Affiliated Hospital of Sun Yat-sen University.

Keywords

Animal model; Diethylnitrosamine; Hepatocellular carcinoma (HCC); microRNA-26a; Nanoparticles; alanine aminotransferase; albumin; alkaline phosphatase; alpha fetoprotein; arginase 1; aspartate aminotransferase; bilirubin; caspase 3; cyclin D1; decarboxyprothrombin; DNA methyltransferase 3B; gamma glutamyltransferase; Ki 67 antigen; microRNA 26a; nanocarrier; transforming growth factor beta; tumor necrosis factor; vasculotropin; alanine aminotransferase blood level; albumin blood level; alpha fetoprotein blood level; animal experiment; animal tissue; Article; aspartate aminotransferase blood level; Bagg albino mouse; bilirubin blood level; biochemical analysis; body weight gain; carcinogenesis; cell viability; controlled study; cytotoxicity; down regulation; drug delivery system; drug efficacy; encapsulation; enzyme linked immunosorbent assay; experimental design; gamma glutamyl transferase blood level; genetic screening; Hep-G2 cell line; histopathology; human; human cell; immunohistochemistry; liver cell carcinoma; liver tissue; male; mouse; mouse model; nonhuman; upregulation

Citation Information

Scopus Citations: 2

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