论文标题: |
Polarization of Tumor-Associated Macrophages Promoted by Vitamin C-Loaded Liposomes for Cancer Immunotherapy |
作者: |
Ma, Zhaoyu; Yang, Mingkun; Foda, Mohamed Frahat; Zhang, Kai; Li, Shuting; Liang, Huageng; Zhao, Yanli; Han, Heyou |
出版刊物: |
ACS NANO |
出版日期: |
OCT 25 |
出版年份: |
2022 |
卷/期: |
|
DOI: |
10.1021/acsnano.2c08446 |
论文摘要: |
While checkpoint blockade immunotherapy as a promising clinical modality has revolutionized cancer treat-ment, it is of benefit to only a subset of patients because of the tumor immunosuppressive microenvironment. Herein, we report that the specified delivery of vitamin C at the tumor site by responsive lipid nanoparticles can efficiently induce oxidative toxicity and the polarization of M1 macrophages, promoting the infiltration of activating cytotoxic T lymphocytes in the tumor microenvironment for intensive immune checkpoint blocking therapy. Both in vitro and in vivo assays demonstrate successful vitamin C-induced polarization of M2 macrophages to M1 macrophages. In vivo transcriptome analysis also reveals the activation mechanism of vitamin C immunity. More importantly, the combination approach displays much better immune response and immune process within the tumor microenvironment than clinical programmed cell death ligand 1 (Anti-PD-L1) alone. This work provides a powerful therapeutic application of vitamin C to amplify Anti-PD-L1 immunotherapy in cancer treatment, which brings hope to patients with clinically insensitive immunity. |