Polarization of tumor-associated macrophages promoted by vitamin C-loaded liposomes for cancer immunotherapy

• Main Authors: Ma, Zhaoyu, Yang, Mingkun, Foda, Mohamed Frahat, Zhang, Kai, Li, Shuting, Liang, Huageng, Zhao, Yanli, Han, Heyou
• Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
• Format: Article
• Language: English
• Published: 2023
• Subjects: Engineering::Bioengineering; Checkpoint Blockade Immunotherapy; Macrophage Polarization
• Online Access: https://hdl.handle.net/10356/170510
• Institution: Nanyang Technological University

While checkpoint blockade immunotherapy as a promising clinical modality has revolutionized cancer treatment, 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.