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Oxygen‐Generating Cryogels Restore T Cell Mediated Cytotoxicity in Hypoxic Tumors
Author(s) -
Colombani Thibault,
Eggermont Loek J.,
Hatfield Stephen M.,
Rogers Zachary J.,
Rezaeeyazdi Mahboobeh,
Memic Adnan,
Sitkovsky Michail V.,
Bencherif Sidi A.
Publication year - 2021
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202102234
Subject(s) - cytotoxicity , materials science , oxygen , reactive oxygen species , cancer research , biophysics , nanotechnology , microbiology and biotechnology , biology , in vitro , biochemistry , chemistry , organic chemistry
Abstract Solid tumors are protected from antitumor immune responses due to their hypoxic microenvironments. Weakening hypoxia‐driven immunosuppression by hyperoxic breathing of 60% oxygen has shown to be effective in unleashing antitumor immune cells against solid tumors. However, efficacy of systemic oxygenation is limited against solid tumors outside of lungs and has been associated with unwanted side effects. As a result, it is essential to develop targeted oxygenation alternatives to weaken tumor hypoxia as novel approaches to restore immune responses against cancer. Herein, injectable oxygen‐generating cryogels (O 2 ‐cryogels) to reverse tumor‐induced hypoxia are reported. These macroporous biomaterials are designed to locally deliver oxygen, inhibit the expression of hypoxia‐inducible genes in hypoxic melanoma cells, and reduce the accumulation of immunosuppressive extracellular adenosine. The data show that O 2 ‐cryogels enhance T cell‐mediated secretion of cytotoxic proteins, restoring the killing ability of tumor‐specific cytotoxic T lymphocytes, both in vitro and in vivo. In summary, O 2 ‐cryogels provide a unique and safe platform to supply oxygen as a coadjuvant in hypoxic tumors and have the potential to improve cancer immunotherapies.