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: [Figure not available: see fulltext.]
CITATION STYLE
Wang, H., Jin, X., Gao, Y., He, X., Xu, Y., Mu, H., … Sun, W. (2023). Reprogramming tumor microenvironment via dual targeting co-delivery of regorafenib and alpha-difluoromethylornithine in osteosarcoma. Cancer Nanotechnology, 14(1). https://doi.org/10.1186/s12645-023-00186-7
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