Enhanced Targeting and Immune Activation of Tumor Microenvironment by Nanomodified Anti-PD1 in Liver Cancer

Liver cancer is one of the most common cancers worldwide, 75% of which are hepatocellular carcinoma (HCC). Generally, chronic inflammation and an immunosuppressive tumor microenvironment are steadily activated in HCC. Although the US Food and Drug Administration (FDA) has approved immune checkpoint inhibitors (ICIs) for use as a clinically advanced HCC treatment, their efficacy in the clinical setting is not satisfactory. Moreover, only a small fraction of antibody reaches the target via systemic circulation due to neutralization of antibodies and off-target delivery. To enhance the localized effects of ICIs, iron oxide nanoparticles (≈10 nm) are conjugated with an antiprogrammed death-1 (anti-PD1) antibody and introduced the ironized antibodies into orthotopic HCC tumors via the systemic circulation. When mice are sacrificed 13 days after the final treatment, mice treated with ironized anti-PD1 significantly regulate tumor-infiltrating leukocytes (TILs), particularly amplifying T-cell functions and recruiting M1 macrophages. More importantly, biochemical indices indicate that mice treated with ironized anti-PD1 recover liver function. This work presents iron oxide nanoparticles integrated with an anti-PD1 antibody that immunomodulates the immunosuppressive tumor microenvironment to generate synergistic effects that achieve tumor inhibition and immune response activation in the context of HCC therapy.