Fibroblast Activation Protein-Targeted Photodynamic Therapy of Cancer-Associated Fibroblasts in Murine Models for Pancreatic Ductal Adenocarcinoma.
Mice
Animals
Cancer-Associated Fibroblasts
Serine Endopeptidases
/ metabolism
Caspase 3
/ metabolism
Tissue Distribution
Disease Models, Animal
Pancreatic Neoplasms
/ metabolism
Carcinoma, Pancreatic Ductal
/ pathology
Fibroblasts
/ metabolism
Antibodies
/ metabolism
Photochemotherapy
Cell Line, Tumor
Pancreatic Neoplasms
cancer-associated fibroblast (CAF)
fibroblast activation protein (FAP)
pancreatic ductal adenocarcinoma (PDAC)
syngeneic models
targeted photodynamic therapy (tPDT)
Journal
Molecular pharmaceutics
ISSN: 1543-8392
Titre abrégé: Mol Pharm
Pays: United States
ID NLM: 101197791
Informations de publication
Date de publication:
07 08 2023
07 08 2023
Historique:
medline:
8
8
2023
pubmed:
24
7
2023
entrez:
24
7
2023
Statut:
ppublish
Résumé
Patients with pancreatic ductal adenocarcinoma (PDAC) have a dismal 5 year survival of 9%. One important limiting factor for treatment efficacy is the dense tumor-supporting stroma. The cancer-associated fibroblasts in this stroma deposit excessive amounts of extracellular matrix components and anti-inflammatory mediators, which hampers the efficacy of chemo- and immunotherapies. Systemic depletion of all activated fibroblasts is, however, not feasible nor desirable and therefore a local approach should be pursued. Here, we provide a proof-of-principle of using fibroblast activation protein (FAP)-targeted photodynamic therapy (tPDT) to treat PDAC. FAP-targeting antibody 28H1 and irrelevant control antibody DP47GS were conjugated to the photosensitizer IRDye700DX (700DX) and the chelator diethylenetriaminepentaacetic acid. In vitro binding and cytotoxicity were evaluated using the fibroblast cell-line NIH-3T3 stably transfected with FAP. Biodistribution of
Identifiants
pubmed: 37485886
doi: 10.1021/acs.molpharmaceut.3c00453
pmc: PMC10410663
doi:
Substances chimiques
Serine Endopeptidases
EC 3.4.21.-
Caspase 3
EC 3.4.22.-
Antibodies
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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