SNAP-Tag Technology Mediates Site Specific Conjugation of Antibody Fragments with a Photosensitizer and Improves Target Specific Phototoxicity in Tumor Cells

Cancer cells can be killed by photosensitizing agents that induce toxic effects when exposed to nonhazardous light, but this also causes significant damage to surrounding healthy cells. The specificity of photodynamic therapy can be increased by conjugating photosensitizing agents to antibodies and...

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Bibliographic Details
Published in:Bioconjugate chemistry 2011-12, Vol.22 (12), p.2487-2495
Main Authors: Hussain, Ahmad Fawzi, Kampmeier, Florian, von Felbert, Verena, Merk, Hans-F, Tur, Mehmet Kemal, Barth, Stefan
Format: Article
Language:English
Subjects:
Cancer
Cell Line, Tumor
Cells
Cytotoxicity
Drug Delivery Systems
Gene Expression
Guanine - analogs & derivatives
Guanine - chemistry
Humans
Neoplasms - drug therapy
Photochemotherapy - methods
Photosensitizing Agents - administration & dosage
Photosensitizing Agents - chemistry
Photosensitizing Agents - pharmacology
Porphyrins - administration & dosage
Porphyrins - chemistry
Porphyrins - pharmacology
Proteins
Receptor, Epidermal Growth Factor - metabolism
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Single-Chain Antibodies - chemistry
Single-Chain Antibodies - genetics
Single-Chain Antibodies - metabolism
Tumors
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Summary:Cancer cells can be killed by photosensitizing agents that induce toxic effects when exposed to nonhazardous light, but this also causes significant damage to surrounding healthy cells. The specificity of photodynamic therapy can be increased by conjugating photosensitizing agents to antibodies and antibody fragments that bind specifically to tumor cell antigens. However, standard conjugation reactions produce heterogeneous products whose targeting specificity and spectroscopic properties can be compromised. In this study, we used an antibody fragment (scFv-425) that binds to the epidermal growth factor receptor (EGFR) as a model to investigate the use of SNAP-tag fusions as an improved conjugation strategy. The scFv-425-SNAP-tag fusion protein allowed the specific conjugation of a chlorin e6 photosensitizer modified with O(6)-benzylguanine, generating a homogeneous product that was delivered specifically to EGFR+ cancer cells and resulted in significant, tumor cell-specific cytotoxicity. The impact of our results on the development of photodynamic therapy is discussed.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc200304k