Volume-2 ,Issue-7, July- 2026

Hepatocellular carcinoma (HCC) remains the predominant histological subtype of primary liver cancer and is characterized by high mortality, frequent late diagnosis, extensive molecular heterogeneity, and limited durable responses to systemic therapy. Resveratrol, a polyphenolic stilbene abundant in grapes, berries, and peanuts, has attracted major attention in HCC research because it modulates apoptosis, oxidative stress, inflammation, epithelial-mesenchymal transition, angiogenesis, autophagy, and oncogenic signaling networks including PI3K/Akt/mTOR, Wnt/β-catenin, NF-κB, and MAPK. However, the translational impact of free resveratrol is constrained by poor aqueous solubility, rapid metabolism, chemical instability, and very low systemic bioavailability, all of which limit intratumoral exposure and therapeutic persistence. Lipid nanocarriers including liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanoemulsions, micelles, and lipid-polymer hybrid nanoparticles offer a rational strategy to overcome these barriers through improved encapsulation, protection from degradation, prolonged circulation, controlled release, and tumor-selective accumulation. Emerging evidence indicates that lipid nanocarrier formulations enhance resveratrol stability, cellular uptake, and biological potency, and may enable combination treatment, ligand-directed targeting, and modulation of multidrug resistance and the tumor microenvironment in liver cancer. This review synthesizes current knowledge on HCC pathobiology, the anticancer pharmacology of resveratrol, the design principles of lipid nanocarriers, and the recent progress in resveratrol-loaded lipid systems relevant to HCC. It further discusses uptake mechanisms, intracellular trafficking, tumor microenvironment interactions, translational challenges, and future opportunities including stimuli-responsive systems, exosome-lipid hybrids, AI-assisted formulation design, and personalized nanomedicine approaches.

Keyword: Hepatocellular carcinoma; resveratrol; lipid nanocarriers; tumor microenvironment; targeted delivery; nanomedicine.