Activating Iterative Revolutions of the Cancer-Immunity Cycle in Hypoxic Tumors with a Smart Nano-Regulator
© 2024 Wiley‐VCH GmbH.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 29 vom: 09. Juli, Seite e2400196 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2024
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| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article activatable nano‐regulator cancer immunity cycle hypoxic tumor therapy immune resistance Photosensitizing Agents Triazoles (+)-JQ1 compound Azepines Polyethylene Glycols mehr... |
| Zusammenfassung: | © 2024 Wiley‐VCH GmbH. The activation of sequential events in the cancer-immunity cycle (CIC) is crucial for achieving effective antitumor immunity. However, formidable challenges, such as innate and adaptive immune resistance, along with the off-target adverse effects of nonselective immunomodulators, persist. In this study, a tumor-selective nano-regulator named PNBJQ has been presented, focusing on targeting two nonredundant immune nodes: inducing immunogenic cancer cell death and abrogating immune resistance to fully activate endogenous tumor immunity. PNBJQ is obtained by encapsulating the immunomodulating agent JQ1 within a self-assembling system formed by linking a Type-I photosensitizer to polyethylene glycol through a hypoxia-sensitive azo bond. Benefiting from the Type-I photosensitive mechanism, PNBJQ triggers the immunogenic cell death of hypoxic tumors under near-infrared (NIR) light irradiation. This process resolves innate immune resistance by stimulating sufficient cytotoxic T-lymphocytes. Simultaneously, PNBJQ smartly responds to the hypoxic tumor microenvironment for precise drug delivery, adeptly addressing adaptive immune resistance by using JQ1 to downregulate programmed death ligand 1 (PD-L1) and sustaining the response of cytotoxic T lymphocytes. The activatable synergic photoimmunotherapy promotes an immune-promoting tumor microenvironment by activating an iterative revolution of the CIC, which remarkably eradicates established hypoxic tumors and suppresses distal lesions under low light dose irradiation |
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| Beschreibung: | Date Completed 18.07.2024 Date Revised 18.07.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202400196 |