Redefining hepatocellular carcinoma treatment: nanotechnology meets tumor immune microenvironment

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide, characterised by its complex pathogenesis and poor therapeutic outcomes. Despite recent advances in targeted molecular therapies, immune checkpoint inhibitors (ICIs), radiotherapy and conventional chemotherapy, the 5-year survival rate for this neoplasm remains dismally low. The progress in nanotechnology has revolutionised cancer treatment in recent years. These advances provide unprecedented opportunities to overcome the current limitations of different therapeutic modalities. This review provides a comprehensive analysis of how nanotechnology interfaces with the tumour immune microenvironment (TIME) in HCC and can present a new frontier in therapeutic interventions for HCC. We critically overview the latest developments in nanoparticle-based delivery systems for various drugs and also other antitumor agents like thermal therapy and radiotherapy. We also highlight the unique ability of nanoparticles to modulate the immunosuppressive tumour microenvironment (TME) and enhance therapeutic efficacy. Furthermore, we analyse emerging strategies that exploit nanoformulations to overcome biological barriers and enhance drug bioavailability in HCC treatment.