4.7 Article

Epidermal growth factor receptor-targeted photosensitizer selectively inhibits EGFR signaling and induces targeted phototoxicity in ovarian cancer cells

期刊

CANCER LETTERS
卷 321, 期 2, 页码 120-127

出版社

ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2012.01.014

关键词

Ovarian cancer; Photodynamic therapy; Cetuximab; Verteporfin; Immunoconjugate

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资金

  1. National Institutes of Health [RO1AR40352, 5R01CA160998, PO1CA84203]
  2. Massachusetts Department of Public Health [34081126112]
  3. Whitaker Foundation

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Targeted photosensitizer delivery to EGFR-expressing cells was achieved in the present study using a high purity, targeted photoimmunoconjugate (PIC). When the PDT agent, benzoporphyrin derivative monoacid ring A (BPD) was coupled to an EGFR-targeting antibody (cetuximab), we observed altered cellular localization and selective phototoxicity of EGFR-positive cells, but no phototoxicity of EGFR-negative cells. Cetuximab in the PIC formulation blocked EGF-induced activation of the EGFR and downstream signaling pathways. Our results suggest that photoimmunotargeting is a useful dual strategy for the selective destruction of cancer cells and also exerts the receptor-blocking biological function of the antibody. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

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