Modifications of microvascular EC surface modulate phototoxicity of a porphycene anti-ICAM-1 immunoconjugate; therapeutic implications.

Abstract

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.

• Authors: Elisabet Rosàs, Pablo Santomá, Miquel Duran-Frigola, Bryan Hernandez, Maria C Llinàs, Rubén Ruiz-González, Santi Nonell, David Sánchez-García, Elazer R Edelman, Mercedes Balcells
• Journal: Langmuir : the ACS journal of surfaces and colloids (Langmuir) Vol. 29 Issue 31 Pg. 9734-43 (Aug 06 2013) ISSN: 1520-5827 [Electronic] United States
• PMID: 23844929 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoconjugates
• Photosensitizing Agents
• Porphyrins
• porphycene
• Intercellular Adhesion Molecule-1

Topics

• Cells, Cultured
• Endothelial Cells (drug effects, immunology)
• Humans
• Immunoconjugates (immunology)
• Immunotherapy
• Intercellular Adhesion Molecule-1 (immunology)
• Microvessels (cytology)
• Photosensitizing Agents (chemical synthesis, chemistry, pharmacology)
• Porphyrins (pharmacology)
• Surface Properties