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A Self-Delivery Nanodrug Simultaneously Inhibits COX-2/PGE 2 Mediated Inflammation and Downregulates PD-L1 to Boost Photoimmunotherapy.
- Source :
-
Advanced healthcare materials [Adv Healthc Mater] 2024 Aug; Vol. 13 (20), pp. e2400367. Date of Electronic Publication: 2024 May 05. - Publication Year :
- 2024
-
Abstract
- Phototherapy promotes anti-tumor immunity by inducing immunogenic cell death (ICD), However, the accompanying inflammatory responses also trigger immunosuppression, attenuating the efficacy of photo-immunotherapy. Herein, they co-assembled a cell-membrane targeting chimeric peptide C16-Cypate-RRKK-PEG <subscript>8</subscript> -COOH (CCP) and anti-inflammatory diclofenac (DA) to develop a nanodrug (CCP@DA) that both enhances the immune effect of phototherapy and weakens the inflammation-mediated immunosuppression. CCP@DA achieves cell membrane-targeting photodynamic and photothermal synergistic therapies to damage programmed death ligand 1 (PD-L1) and induce a strong ICD to activate anti-tumor response. Simultaneously, the released DA inhibits the cycoperoxidase-2 (COX-2)/prostaglandin E2 (PGE <subscript>2</subscript> ) pathway in tumor cells to inhibit pro-tumor inflammation and further down-regulate PD-L1 expression to relieve the immunosuppressive microenvironment. CCP@DA significantly inhibited tumor growth and inflammation both in vitro and in vivo, while maintaining a potent anti-tumor immune response. Additionally, it exhibits excellent anti-metastatic capabilities and prolongs mouse survival time with a single dose and low levels of near-infrared (NIR) light exposure. This work provides a valuable strategy to control the therapy-induced inflammation for high-efficiency photoimmunotherapy.<br /> (© 2024 Wiley‐VCH GmbH.)
- Subjects :
- Animals
Mice
Cell Line, Tumor
Humans
Diclofenac pharmacology
Diclofenac administration & dosage
Phototherapy methods
Nanoparticles chemistry
Down-Regulation drug effects
Photochemotherapy methods
B7-H1 Antigen metabolism
Dinoprostone metabolism
Immunotherapy methods
Cyclooxygenase 2 metabolism
Inflammation
Subjects
Details
- Language :
- English
- ISSN :
- 2192-2659
- Volume :
- 13
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Advanced healthcare materials
- Publication Type :
- Academic Journal
- Accession number :
- 38704750
- Full Text :
- https://doi.org/10.1002/adhm.202400367