Reprogramming tumor microenvironment via dual targeting co-delivery of regorafenib and alpha-difluoromethylornithine in osteosarcoma

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) vascular aberrations in TME. TME reprogramming a promising therapeutic approach for treating tumors. Anti-angiogenesis has power to control polarization of macrophages, prevent progression, increase drug penetration. Additionally, polyamine blocking therapy can CD8 + T cell infiltration decrease immunosuppressive cells. These results led developing potential regimen that targets TAMs angiogenesis reprogram osteosarcoma Results For targeted biomimetic co-delivery regorafenib alpha-difluoromethylornithine via mannose receptor, which overexpressed cells, mannosylated poly(lactide-co-glycolide)-polyethylene glycol nanoparticles (Man-NPs) were synthesized. The superior physiological properties intratumoral accumulation Man-NPs efficiently promoted inhibited angiogenesis. Macrophage repolarization further activated immune contributed remodeling Conclusion Overall, these findings suggested using as an immunotherapeutic treat may be promising. Graphical