PFC@O₂ Targets HIF-1α to Reverse the Immunosuppressive TME in OSCC

As a typical hallmark of solid tumors, hypoxia affects the effects of tumor radiotherapy, chemotherapy, and photodynamic therapy. Therefore, targeting the hypoxic tumor microenvironment (TME) is a promising treatment strategy for cancer therapy. Here, we prepared an Albumin Human Serum (HSA)-coated perfluorocarbon (PFC) carrying oxygen (PFC@O₂) to minimize OSCC hypoxia. The results showed that PFC@O₂ significantly downregulated the expression of HIF-1α and the number of M2-like macrophages in vitro. Furthermore, PFC@O₂ effectively inhibited the growth of oral squamous cell carcinoma (OSCC) and reduced the proportion of negative immunoregulatory cells, including myeloid-derived suppressor cells (MDSCs) and M2-like macrophages of TME in a 4-nitroquinoline N-oxide (4NQO)-induced mouse model. Conversely, the infiltration of CD4⁺ and CD8⁺ T cells was significantly increased in TME, suggesting that the anti-tumor immune response was enhanced. However, we also found that hypoxia-relative genes expression was positively correlated with CD68⁺/CD163⁺ TAMs in human tissue specimens. In summary, PFC@O₂ could effectively inhibit the progression of OSCC by alleviating hypoxia, which provides a practical basis for gas therapy and gas synergistic therapy for OSCC.