Comprehensive insights of etiological drivers of hepatocellular carcinoma: Fostering targeted nano delivery to anti-cancer regimes.

Hepatocellular carcinoma (HCC) stands as one of the most prevalent and deadliest malignancies on a global scale. Its complex pathogenesis arises from multifactorial etiologies, including viral infections, metabolic syndromes, and environmental carcinogens, all of which drive genetic and molecular aberrations in hepatocytes. This intricate condition is associated with multiple causative factors, resulting in the abnormal activation of various cellular and molecular pathways. Given that HCC frequently manifests within the context of a compromised or cirrhotic liver, coupled with the tendency of late-stage diagnoses, the overall prognosis tends to be unfavorable. Systemic therapy, especially conventional cytotoxic drugs, generally proves ineffective. Despite advancements in therapeutic interventions, conventional treatments such as chemotherapy often exhibit limited efficacy and substantial systemic toxicity. In this context, nanomedicine, particularly lipid-based nanoparticles (LNPs), has emerged as a promising strategy for enhancing drug delivery specificity and reducing adverse effects. This review provides a comprehensive overview of the molecular and metabolic underpinnings of HCC. Furthermore, we explored the role of lipid-based nano-formulations including liposomes, solid lipid nanoparticles, and nanostructured lipid carriers in targeted drug delivery for HCC. We have highlighted recent advances in LNP-based delivery approaches, FDA-approved drugs, and surface modification strategies to improve liver-specific delivery and therapeutic efficacy. It will provide a comprehensive summary of various treatment strategies, recent clinical advances, receptor-targeting strategies and the role of lipid composition in cellular uptake. The review concludes with a critical assessment of existing challenges and future prospects in nanomedicines-driven HCC therapy.