Self-delivery photodynamic-hypoxia alleviating nanomedicine synergizes with anti-PD-L1 for cancer immunotherapy

Abstract

The low level of T-lymphocyte infiltration in tumor is a key issue in cancer immunotherapy. Stimulating anti-tumor immune responses and improving the tumor microenvironment are essential for enhancing anti-PD-L1 immunotherapy. Herein, atovaquone (ATO), protoporphyrin IX (PpIX), and stabilizer (ATO/PpIX NPs) were constructed to self-assemble with hydrophobic interaction and passively targeted to tumor for the first time. The studies have indicated that PpIX-mediated photodynamic induction of immunogenic cell death combined with relieving tumor hypoxia by ATO, leading to maturation of dendritic cells, polarization of M2-type tumor-associated macrophages (TAMs) towards M1-type TAMs, infiltration of cytotoxic T lymphocytes, reduction of regulatory T cells, release of pro-inflammatory cytokines, resulting in an effective anti-tumor immune response synergized with anti-PD-L1 against primary tumor and pulmonary metastasis. Taken together, the combined nanoplatform may be a promising strategy to enhance cancer immunotherapy.

Keywords: Anti-PD-L1 therapy; Cancer immunotherapy; Hypoxic microenvironment; Immunogenetic cell death; Tumor-associated macrophages.