دورية أكاديمية
Fibroblast Activation Protein-Targeting Minibody-IRDye700DX for Ablation of the Cancer-Associated Fibroblast with Photodynamic Therapy
| العنوان: | Fibroblast Activation Protein-Targeting Minibody-IRDye700DX for Ablation of the Cancer-Associated Fibroblast with Photodynamic Therapy |
|---|---|
| المؤلفون: | Esther M. M. Smeets, Daphne N. Dorst, Gerben M. Franssen, Merijn S. van Essen, Cathelijne Frielink, Martijn W. J. Stommel, Marija Trajkovic-Arsic, Phyllis F. Cheung, Jens T. Siveke, Ian Wilson, Alessandro Mascioni, Erik H. J. G. Aarntzen, Sanne A. M. van Lith |
| المصدر: | Cells; Volume 12; Issue 10; Pages: 1420 |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute |
| سنة النشر: | 2023 |
| المجموعة: | MDPI Open Access Publishing |
| مصطلحات موضوعية: | minibody, targeted photodynamic therapy (tPDT), cancer-associated fibroblast (CAF), fibroblast activation protein (FAP), pancreatic ductal adenocarcinoma (PDAC) |
| الوصف: | 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. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Cell Proliferation and Division; https://dx.doi.org/10.3390/cells12101420Test |
| DOI: | 10.3390/cells12101420 |
| الإتاحة: | https://doi.org/10.3390/cells12101420Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.491E1FA6 |
| قاعدة البيانات: | BASE |
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