title: 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.affiliation: Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Rosàs
authors.forename: Pablo
authors.initials: P
authors.lastname: Santomá
authors.forename: Miquel
authors.initials: M
authors.lastname: Duran-Frigola
authors.forename: Bryan
authors.initials: B
authors.lastname: Hernandez
authors.forename: Maria C
authors.initials: MC
authors.lastname: Llinàs
authors.forename: Rubén
authors.initials: R
authors.lastname: Ruiz-González
authors.forename: Santi
authors.initials: S
authors.lastname: Nonell
authors.forename: David
authors.initials: D
authors.lastname: Sánchez-García
authors.forename: Elazer R
authors.initials: ER
authors.lastname: Edelman
authors.forename: Mercedes
authors.initials: M
authors.lastname: Balcells
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology*; D007167:Immunotherapy; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D055806:Microvessels / Q000166:cytology; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D013499:Surface Properties
chemical_list: D018796:Immunoconjugates; D017319:Photosensitizing Agents; D011166:Porphyrins; C051407:porphycene; D018799:Intercellular Adhesion Molecule-1