Second Near-Infrared Light-Activatable Polymeric Nanoantagonist for Photothermal Immunometabolic Cancer Therapy.
Animals
Apoptosis
/ radiation effects
Caspase 3
/ metabolism
Cell Line, Tumor
Humans
Hyperthermia, Induced
Immunotherapy
Infrared Rays
Mice
Nanostructures
/ chemistry
Neoplasms
/ radiotherapy
Photothermal Therapy
Polymers
/ chemistry
Semiconductors
Signal Transduction
T-Lymphocytes, Cytotoxic
/ drug effects
Theranostic Nanomedicine
cancer therapy
photoactivation
polymer nanoparticles
second near-infrared photothermal therapy
Journal
Advanced materials (Deerfield Beach, Fla.)
ISSN: 1521-4095
Titre abrégé: Adv Mater
Pays: Germany
ID NLM: 9885358
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
revised:
27
04
2021
received:
19
02
2021
pubmed:
24
7
2021
medline:
19
1
2022
entrez:
23
7
2021
Statut:
ppublish
Résumé
Immunometabolic modulation offers new opportunities to treat cancers as it is highly associated with cancer progression and immunosuppressive microenvironment. However, traditional regimens using nonselective small-molecule immunomodulators lead to the off-target adverse effects and insufficient therapeutic outcomes. Herein a second near-infrared (NIR-II) photothermally activatable semiconducting polymeric nanoantagonist (ASPA) for synergistic photothermal immunometabolic therapy of cancer is reported. ASPA backbone is obtained by conjugating vipadenant, an antagonist to adenosine A2A receptor, onto NIR-II light-absorbing semiconducting polymer via an azo-based thermolabile linker. Under deep-penetrating NIR-II photoirradiation, ASPA induces tumor thermal ablation and subsequently immunogenic cell death, triggers the cleavage of thermolabile linker, and releases the antagonist to block the immunosuppressive adenosinergic pathway. Such a remotely controlled immunometabolic regulation potentiates cytotoxic T cell functions while suppresses regulatory T cell activities, leading to efficient primary tumor inhibition, pulmonary metastasis prevention, and long-term immunological memory. Thereby, this work provides a generic polymeric approach for precise spatiotemporal regulation of cancer immunometabolism.
Identifiants
pubmed: 34296785
doi: 10.1002/adma.202101410
doi:
Substances chimiques
Polymers
0
Caspase 3
EC 3.4.22.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2101410Subventions
Organisme : Ministry of Education, Academic Research Fund Tier 1
ID : 2019-T1-002-045
Organisme : Ministry of Education, Academic Research Fund Tier 1
ID : RG125/19
Organisme : Academic Research Fund Tier 2
ID : MOE2018-T2-2-042
Organisme : A*STAR SERC AME Programmatic Fund
ID : SERC A18A8b0059
Informations de copyright
© 2021 Wiley-VCH GmbH.
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