Oxygen-carrying nanoplatform to reprogram tumor immunosuppressive microenvironment and enhance photothermal-immunotherapy

Abstract

Immunotherapy shows great promise on treating tumors. However, insufficient antigen exposure and immunosuppressive tumor microenvironment (TME) caused by hypoxia impose a serial of constraints on the therapeutic efficacy. In this study, we developed an oxygen-carrying nanoplatform loaded with perfluorooctyl bromide (PFOB, a second-generation of perfluorocarbon-based blood substitute), IR780 (a photosensitizer) and imiquimod (R837, an immune adjuvant) to reprogram immunosuppressive TME and reinforce photothermal-immunotherapy. The obtained oxygen-carrying nanoplatforms (abbreviated as IR-R@LIP/PFOB) show highly efficient oxygen release behavior and excellent hyperthermia performance upon laser irradiation, thus achieving the attenuation of the inherent tumor hypoxia and the exposure of tumor associated antigens in situ, and transforming the immunosuppressive TME to an immunosupportive one. We found that the photothermal therapy of IR-R@LIP/PFOB together with anti-programmed cell death protein-1 (anti-PD-1) would elicit a robust antitumor immunity by increasing the tumor-infiltrating frequencies of cytotoxic CD8+ T cells and tumoricidal M1-phenotype macrophages, while reducing immunosuppressive M2-phenotype macrophages and regulatory T cells (Tregs). This study presents these oxygen-carrying IR-R@LIP/PFOB nanoplatforms are potent in removing some negative impacts of immunosuppressive TME caused by hypoxia, and suppressing tumor growth by initiating antitumor immune responses, especially in combination with anti-PD-1 immunotherapy.

Keywords

• Hypoxia
• Tumor immunosuppressive microenvironment
• Photothermal-immunotherapy
• Nanomedicine