Dual Oxygen-Supply Immunosuppression-Inhibiting Nanomedicine to Avoid the Intratumoral Recruitment of Myeloid-Derived Suppressor Cells.

Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 101235338 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1613-6829 (Electronic) Linking ISSN: 16136810 NLM ISO Abbreviation: Small Subsets: MEDLINE

Original Publication: Weinheim, Germany : Wiley-VCH, c2005-

Myeloid-Derived Suppressor Cells*/drug effects ; Myeloid-Derived Suppressor Cells*/metabolism ; Nanomedicine*/methods ; Oxygen*/chemistry ; Tumor Microenvironment*/drug effects; Animals ; Humans ; Cell Line, Tumor ; Immunosuppression Therapy ; Fluorocarbons/chemistry ; Mice ; Hydrocarbons, Brominated

Myeloid-derived suppressor cells (MDSCs) are reported to be responsible for the negative prognosis of colorectal cancer (CRC) patients due to the mediated immunosuppressive tumor microenvironment (TME). The selective and chronic circumvention of tumor-infiltrated MDSCs has potential clinical significance for CRC treatment, which unluckily remains a technical challenge. Because tumor hypoxia makes a significant contribution to the recruitment of MDSCs in tumor sites, a dual oxygen-supplied immunosuppression-inhibiting nanomedicine (DOIN) is demonstrated for overcoming tumor hypoxia, which achieves selective and long-term inhibition of intratumoral recruitment of MDSCs. The DOIN is constructed by the encasement of perfluorooctyl bromide (PFOB) and 4-methylumbelliferone (4-MU) into a TME-responsive amphiphilic polymer. This nanoplatform directly carries oxygen to the tumor region and simultaneously loosens the condensed tumor extracellular matrix for the normalization of tumor vasculature, which selectively remodels the TME toward one adverse to the intratumoral recruitment of MDSCs. Importantly, this nanoplatform offers a long-acting alleviation of the hypoxic TME, chronically avoiding the comeback of tumor-infiltrated MDSCs. Consequently, the immunosuppressive TME is relieved, and T cells are successfully proliferated and activated into cytotoxic T lymphocytes, which boosts a systemic immune response and contributes to lasting inhibition of tumor growth with a prolonged survival span of xenograft.
(© 2024 Wiley‐VCH GmbH.)

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2023A1515012452 Guangdong Basic and Applied Basic Research Foundation; 2024B03J0022 Science and Technology Program of Guangzhou; 82473154,81970500 National Natural Science Foundation of China

Keywords: colorectal cancer; enhanced immunoreactivity; hypoxic tumor microenvironment; myeloid‐derived suppressor cells; nanoplatform

S88TT14065 (Oxygen)
0 (Fluorocarbons)
Q1D0Q7R4D9 (perflubron)
0 (Hydrocarbons, Brominated)

Date Created: 20240905 Date Completed: 20241127 Latest Revision: 20241127

20241202

10.1002/smll.202406860

39233543