Journal
JOURNAL OF CONTROLLED RELEASE
Volume 309, Issue -, Pages 82-93Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2019.07.028
Keywords
Hypoxia alleviation; Photodynamic therapy; Immunotherapy; Anti-metastasis; Hydrogel
Funding
- National Science and Technology Major Project [2017YFA0205400]
- National Natural Science Foundation of China [81773667, 81573369]
- NSFC Projects of International Cooperation and Exchanges [81811540416]
- Outstanding Youth Fund of Jiangsu Province of China [BK20160031]
- Fundamental Research Funds for the Central Universities [2632018PT01, 2632018ZD12]
- Ministry of Education of China
- State Administration of Foreign Experts Affairs of China [B16046]
- Double first-class project [CPU2018GY06]
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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)-1 alpha 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.
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