Inhibition of breast cancer proliferation and metastasis by strengthening host immunity with a prolonged oxygen-generating phototherapy hydrogel

Tian-Jiao, Zhou, Lei, Xing, Ya-Tong, Fan, Peng-Fei, Cui, Hu-Lin, Jiang

Journal of Controlled Release |

Hypoxia is a potent tumor microenvironmental (TME) factor promoting immunosuppression and metastatic progression. For current anticancer therapeutic strategies, the combination of hypoxia alleviation and photodynamic therapy (PDT) might be a useful approach to further improve anticancer efficacy. In this study, we alleviated tumor hypoxia using a prolonged oxygen-generating phototherapy hydrogel (POP-Gel), which effectively elevated the oxygen level and shrank the hypoxic regions of tumors for up to 5 days evaluated by photoacoustic (PA) imaging and immunofluorescence staining, meeting the requirement of the “once injection, sustained treatment” strategy and significantly increasing PDT efficacy. The long-period improvement of the tumor hostile environment downregulated the expression of hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF), further preventing tumor growth and metastasis. More importantly, the enhanced PDT triggered a more intense immune response, improving the inhibition of triple negative breast cancer growth even tumor elimination. The POP-Gel may contribute useful insights into the combination of hypoxia alleviation and PDT.