Synergistic strategies combining nanomaterial-based oxygen modulation and immunotherapy for hepatocellular carcinoma

Hepatocellular Carcinoma (HCC) remains one of the leading causes of death across the world due to late diagnosis, unresponsiveness to treatment, and poor prognosis. The presence of a hypoxic tumor microenvironment (TME) plays an essential role in the development and progression of HCC, contributing to tumor angiogenesis, metabolic remodeling, and profound immunosuppression. Hypoxic conditions not only inhibit the activity of cytotoxic T-cells but also favor the development of tumor immunity evasion mechanisms. In light of these findings, the employment of nanomaterial-mediated oxygen delivery technologies has gained popularity due to their ability to reduce hypoxia and enhance immune response. Nanotechnologies, including oxygen-generating nanoplatforms and oxygen carriers, allow altering the composition of the TME to boost the effectiveness of treatment approaches. Current studies indicate that the combination of nanotechnology and immuno-therapeutic approaches, including immune checkpoint inhibitors, CAR-T cell therapies, and cancer vaccines, leads to a significant enhancement of the antitumor effect. These strategies have shown marked regression of the tumors and an increase in life span from the preclinical results. However, there are some issues associated with biosafety, delivery, and clinical applicability. This new strategy, where oxygen-modifying nanoparticles can be combined with immunotherapy, marks a new future for HCC management.