SNAP-Tag Technology Mediates Site Specific Conjugation of Antibody Fragments with a Photosensitizer and Improves Target Specific Phototoxicity in Tumor Cells
SNAP-Tag Technology Mediates Site Specific Conjugation of Antibody Fragments with a Photosensitizer and Improves Target Specific Phototoxicity in Tumor Cells
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DOI：
10.1021/bc200304k
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发表时间：
2011-12-01
影响因子：
4.7
通讯作者：
Barth, Stefan
中科院分区：
文献类型：
--
作者：
Hussain, Ahmad Fawzi;Kampmeier, Florian;Barth, Stefan
癌细胞可以被光敏剂杀死，当暴露在无害的光下时，光敏剂会引起毒性作用，但这也会对周围的健康细胞造成重大损害。光动力疗法的特异性可以通过将光敏剂偶联到特异性结合肿瘤细胞抗原的抗体和抗体片段上来提高。然而，标准的偶联反应产生非均相产物，其靶向特异性和光谱性质可能受到损害。在这项研究中，我们使用结合表皮生长因子受体（EGFR）的抗体片段（scFv-425）作为模型来研究snap标签融合作为一种改进的偶联策略的使用。scfv - 42s - snaptag融合蛋白允许与O(6)-苄基鸟嘌呤修饰的氯e6光敏剂特异性结合，产生一种均匀的产物，特异性递送到EGFR（+）癌细胞，并产生显著的肿瘤细胞特异性细胞毒性。讨论了本研究结果对光动力疗法发展的影响。
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-42S-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.