Research
| Title： | Polarization of Tumor-Associated Macrophages Promoted by Vitamin C-Loaded Liposomes for Cancer Immunotherapy |
|---|---|
| First author： | Ma, Zhaoyu; Yang, Mingkun; Foda, Mohamed Frahat; Zhang, Kai; Li, Shuting; Liang, Huageng; Zhao, Yanli; Han, Heyou |
| Journal： | ACS NANO |
| Years： | 2022 |
| DOI： | 10.1021/acsnano.2c08446 |
| Abstract： | 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. |
