Modifications of Microvascular EC Surface Modulate Phototoxicity of a Porphycene anti-ICAM-1 Immunoconjugate; Therapeutic Implications
| Autor: | Pablo Santomá, Elazer R. Edelman, Santi Nonell, Bryan Hernandez, Rubén Ruiz-González, Elisabet Rosas, Miquel Duran-Frigola, Mercedes Balcells, Maria C. Llinàs, David Sánchez-García |
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| Rok vydání: | 2013 |
| Předmět: |
Immunoconjugates
Porphyrins Endothelium Surface Properties Stereochemistry medicine.medical_treatment Photodynamic therapy Inflammation Article Electrochemistry medicine Humans General Materials Science Cells Cultured Spectroscopy ICAM-1 Photosensitizing Agents Cell adhesion molecule Chemistry Endothelial Cells Surfaces and Interfaces Immunotherapy Intercellular Adhesion Molecule-1 Condensed Matter Physics Immunoconjugate medicine.anatomical_structure Microvessels Cancer research medicine.symptom Phototoxicity |
| Zdroj: | Langmuir. 29:9734-9743 |
| ISSN: | 1520-5827 0743-7463 |
| Popis: | Inflammation and shear stress can upregulate expression of cellular adhesion molecules in endothelial cells (EC). The modified EC surface becomes a mediating interface between the circulating blood elements and the endothelium, and grants opportunity for immunotherapy. In photodynamic therapy (PDT), immunotargeting might overcome the lack of selectivity of currently used sensitizers. In this study, we hypothesized that differential ICAM-1 expression modulates the effects of a drug targeted to surface ICAM-1. A novel porphycene-anti-ICAM-1 conjugate was synthesized and applied to treat endothelial cells from macro and microvasculature. Results show that the conjugate induces phototoxicity in inflamed, but not in healthy, microvascular EC. Conversely, macrovascular EC exhibited phototoxicity regardless of their state. These findings have two major implications; the relevance of ICAM-1 as a modulator of drug effects in microvasculature, and the potential of the porphycene bioconjugate as a promising novel PDT agent. |
| Databáze: | OpenAIRE |
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