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Fibroblast Activation Protein-Targeting Minibody-IRDye700DX for Ablation of the Cancer-Associated Fibroblast with Photodynamic Therapy
- Source :
- Cells; Volume 12; Issue 10; Pages: 1420, Cells, 12, 10, Cells, 12
- Publication Year :
- 2023
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2023.
-
Abstract
- Fibroblast activation protein (FAP), expressed on cancer-associated fibroblasts, is a target for diagnosis and therapy in multiple tumour types. Strategies to systemically deplete FAP-expressing cells show efficacy; however, these induce toxicities, as FAP-expressing cells are found in normal tissues. FAP-targeted photodynamic therapy offers a solution, as it acts only locally and upon activation. Here, a FAP-binding minibody was conjugated to the chelator diethylenetriaminepentaacetic acid (DTPA) and the photosensitizer IRDye700DX (DTPA-700DX-MB). DTPA-700DX-MB showed efficient binding to FAP-overexpressing 3T3 murine fibroblasts (3T3-FAP) and induced the protein’s dose-dependent cytotoxicity upon light exposure. Biodistribution of DTPA-700DX-MB in mice carrying either subcutaneous or orthotopic tumours of murine pancreatic ductal adenocarcinoma cells (PDAC299) showed maximal tumour uptake of 111In-labelled DTPA-700DX-MB at 24 h post injection. Co-injection with an excess DTPA-700DX-MB reduced uptake, and autoradiography correlated with FAP expression in the stromal tumour region. Finally, in vivo therapeutic efficacy was determined in two simultaneous subcutaneous PDAC299 tumours; only one was treated with 690 nm light. Upregulation of an apoptosis marker was only observed in the treated tumours. In conclusion, DTPA-700DX-MB binds to FAP-expressing cells and targets PDAC299 tumours in mice with good signal-to-background ratios. Furthermore, the induced apoptosis indicates the feasibility of targeted depletion of FAP-expressing cells with photodynamic therapy.
- Subjects :
- Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14]
All institutes and research themes of the Radboud University Medical Center
Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14]
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
Medizin
General Medicine
minibody
targeted photodynamic therapy (tPDT)
cancer-associated fibroblast (CAF)
fibroblast activation protein (FAP)
pancreatic ductal adenocarcinoma (PDAC)
Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19]
Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5]
Subjects
Details
- Language :
- English
- ISSN :
- 20734409
- Database :
- OpenAIRE
- Journal :
- Cells; Volume 12; Issue 10; Pages: 1420
- Accession number :
- edsair.doi.dedup.....d44f8e31faa9619bd76ac17bd4aaefbf
- Full Text :
- https://doi.org/10.3390/cells12101420