期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 639, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2023.122970
关键词
Hypoxic microenvironment; Immunogenetic cell death; Anti -PD-L1 therapy; Tumor -associated macrophages; Cancer immunotherapy
The combination of ATO, PpIX and stabilizer (ATO/PpIX NPs) was self-assembled and targeted to tumors for the first time. This combination induced immunogenic cell death, improved the tumor microenvironment, and enhanced the effectiveness of anti-PD-L1 immunotherapy.
The low level of T-lymphocyte infiltration in tumor is a key issue in cancer immunotherapy. Stimulating antitumor 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.
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