Enhancement of Anti-Neoplastic Effects of MGN-3/Biobran Against Solid Ehrlich Carcinoma-Bearing Mice via Lipidic Nanoparticle Based Targeted Drug Delivery System

Abstract

MGN-3 (Biobran), a denatured hemicellulose compound derived from rice bran, possesses potent immunomodulatory and antitumor activity; however, its clinical application is constrained by non-specific tissue distribution, rapid systemic elimination, and poor cellular uptake. To overcome these pharmacological limitations, we engineered MGN-3-loaded lipid nanoparticles (MGN-3.LNPs) formulated with bioactive cinnamon and avocado oils to optimize targeted drug delivery against solid carcinoma. Mice bearing subcutaneous Ehrlich Ascites Carcinoma (EAC) solid tumors received free MGN-3, plain lipid nanoparticles (plain LNPs), or MGN-3.LNPs three times weekly from day 8 to day 26 post-inoculation. The administration of MGN-3.LNPs achieved superior tumor volume suppression (95.00%) compared to free MGN-3 (69.00%) and plain LNPs (63.00%) (p < 0.0001). Mechanistically, MGN-3.LNPs effectively inhibited cancer cell proliferation by suppressing Ki-67 expression while promoting expression shifts that strongly suggest the engagement of mitochondrial-mediated apoptotic signaling, including upregulation of tumor protein p53, Caspase-3, Caspase-9, poly(ADP-ribose) polymerase (PARP), and cytosolic cytochrome c (Cyt c), alongside an elevated Bax/Bcl-2 ratio and reduced 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. Flow cytometric analysis confirmed that MGN-3.LNPs induced marked G0/G1 cell cycle arrest and promoted sub-G1 apoptotic cell accumulation, which was corroborated by Annexin V/propidium iodide (Annexin V/PI) staining and semiquantitative histopathological evaluation. Furthermore, MGN-3.LNPs downregulated the gene expression of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) while restoring redox homeostasis in tumor tissues. Overall, lipidic nanoencapsulation significantly enhances the therapeutic efficacy of MGN-3 against solid tumors through superior nanoscale tissue penetration, prolonged retention, and synergistic lipid–drug bioactivity.