Author:
Wang Hongsheng,Jin Xinmeng,Gao Yinghua,He Xin,Xu Yiming,Mu Haoran,Jiang Yafei,Wang Zhuoying,Yu Chen,Zhang Tao,Hua Yingqi,Cai Zhengdong,Xu Jing,Ma Xiaojun,Sun Wei
Abstract
Abstract
Background
Tumor angiogenesis, immunosuppression, and progression are all closely correlated with the tumor microenvironment (TME). Immune evasion is supported by both M2 phenotype tumor-associated macrophages (TAMs) and vascular aberrations in the TME. TME reprogramming is a promising therapeutic approach for treating tumors. Anti-angiogenesis has the power to control the polarization of macrophages, prevent progression, and increase drug penetration. Additionally, polyamine blocking therapy can increase CD8+ T cell infiltration and decrease immunosuppressive cells. These results led to developing a potential therapeutic regimen that targets TAMs and angiogenesis to reprogram the osteosarcoma TME.
Results
For the targeted biomimetic co-delivery of regorafenib and alpha-difluoromethylornithine via the mannose receptor, which is overexpressed in both TAMs and osteosarcoma cells, mannosylated poly(lactide-co-glycolide)-polyethylene glycol nanoparticles (Man-NPs) were synthesized. The superior physiological properties and intratumoral accumulation of the Man-NPs efficiently promoted TAMs polarization and inhibited angiogenesis. Macrophage repolarization further activated immune cells, which contributed to remodeling the TME.
Conclusion
Overall, these findings suggested that using Man-NPs as an immunotherapeutic approach to treat osteosarcoma may be promising.
Graphical Abstract
Funder
National Natural Science Foundation of China
Shanghai Jiaotong University
Shanghai Pujiang Program
Songjiang District Science and Technology Innovation Fund
Shanghai Rising-Star Program
Publisher
Springer Science and Business Media LLC
Subject
Physical and Theoretical Chemistry,Pharmaceutical Science,Oncology,Biomedical Engineering