VHH-Photosensitizer Conjugates for Targeted Photodynamic Therapy of Met-Overexpressing Tumor Cells
Autor: | Heukers, Raimond, Mashayekhi, Vida, Ramirez-Escudero, Mercedes, de Haard, Hans, Verrips, Theo, van Bergen en Henegouwen, Paul., Oliveira, Sabrina, Sub Cell Biology, Sub Crystal and Structural Chemistry, Afd Pharmaceutics, Celbiologie, Crystal and Structural Chemistry, Pharmaceutics |
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Přispěvatelé: | Sub Cell Biology, Sub Crystal and Structural Chemistry, Afd Pharmaceutics, Celbiologie, Crystal and Structural Chemistry, Pharmaceutics |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy C-Met photosensitizer medicine.medical_treatment Immunology targeted photodynamic therapy Photodynamic therapy VHH hepatocyte growth factor receptor Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Discovery medicine Immunology and Allergy Photosensitizer Epidermal growth factor receptor Receptor c-Met biology HGFR nanobodies 3. Good health 030104 developmental biology chemistry Hepatocyte Growth Factor Receptor 030220 oncology & carcinogenesis Cancer cell biology.protein Cancer research Met Antibody lcsh:RC581-607 |
Zdroj: | Antibodies, 8(2). MDPI AG Antibodies, Vol 8, Iss 2, p 26 (2019) Antibodies Volume 8 Issue 2 |
ISSN: | 2073-4468 |
Popis: | Photodynamic therapy (PDT) is an approach that kills (cancer) cells by the local production of toxic reactive oxygen species upon the local illumination of a photosensitizer (PS). The specificity of PDT has been further enhanced by the development of a new water-soluble PS and by the specific delivery of PS via conjugation to tumor-targeting antibodies. To improve tissue penetration and shorten photosensitivity, we have recently introduced nanobodies, also known as VHH (variable domains from the heavy chain of llama heavy chain antibodies), for targeted PDT of cancer cells overexpressing the epidermal growth factor receptor (EGFR). Overexpression and activation of another cancer-related receptor, the hepatocyte growth factor receptor (HGFR, c-Met or Met) is also involved in the progression and metastasis of a large variety of malignancies. In this study we evaluate whether anti-Met VHHs conjugated to PS can also serve as a biopharmaceutical for targeted PDT. VHHs targeting the SEMA (semaphorin-like) subdomain of Met were provided with a C-terminal tag that allowed both straightforward purification from yeast supernatant and directional conjugation to the PS IRDye700DX using maleimide chemistry. The generated anti-Met VHH-PS showed nanomolar binding affinity and, upon illumination, specifically killed MKN45 cells with nanomolar potency. This study shows that Met can also serve as a membrane target for targeted PDT. |
Databáze: | OpenAIRE |
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