Metabolic modulation via mTOR pathway and anti-angiogenesis remodels tumor microenvironment using PD-L1-targeting codelivery. (October 2020)

• Record Type: Journal Article
• Authors: Chen, Binfan; Gao, Ang; Tu, Bin; Wang, Yonghui; Yu, Xiaolu; Wang, Yingshu; Xiu, Yanfeng; Wang, Bing; Wan, Yakun; Huang, Yongzhuo
• Is Part Of: Biomaterials. Volume 255(2020)
• Publication Date: 2020-10
• Subjects: Tumor-associated macrophage -- Glycolysis -- mTOR -- Angiogenesis -- Tumor immune microenvironment -- Liposome; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2020.120187
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Tumor microenvironment (TME) closely affects cancer progression by promoting cancer cell survival and proliferation, drug resistance, metastasis, and immunosuppression as well. Remodeling TME is a promising therapeutic strategy for anticancer. mTOR signaling is an essential regulator for cellular metabolism and tumor-associated macrophages (TAMs) repolarization. There is an integrated crosstalk among mTOR/metabolism/immunity. Angiogenesis can also regulate metabolism and immunity. Based on these, a potential therapeutic avenue was developed by targeting mTOR and angiogenesis to remodel tumor immune microenvironment (TIME). A dual-targeting delivery liposomal system was designed with dual-modification of PD-L1 nanobody and mannose ligands for co-delivering an mTOR inhibitor (rapamycin) and an anti-angiogenic drug (regorafenib). The liposomes were able to target both TAMs and cancer cells that overexpressed PD-L1 and mannose receptors. The liposomes efficiently reduced glycolysis, repolarized TAMs, inhibited angiogenesis, reprogrammed immune cells, and consequently arrested tumor growth. Graphical abstract: Image 1