Modifications of Microvascular EC Surface Modulate Phototoxicity of a Porphycene anti-ICAM-1 Immunoconjugate; Therapeutic Implications
Author(s)Duran-Frigola, Miquel; Hernandez, Bryan; Nonell, Santi; Edelman, Elazer R.; Fosas, Elisabet; Santoma, Pablo; Llinas, Maria C.; Ruiz-Gonzalez, Ruben; Sanchez-Garcia, David; Balcells-Camps, Mercedes; Rosas, Elisabet; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Institute for Medical Engineering & Science; Harvard University--MIT Division of Health Sciences and Technology
American Chemical Society (ACS)
Rosas, Elisabet, Pablo Santoma, Miquel Duran-Frigola, Bryan Hernandez, Maria C. Llinas, Ruben Ruiz-Gonzalez, Santi Nonell, David Sanchez-Garcia, Elazer R. Edelman, and Mercedes Balcells. “Modifications of Microvascular EC Surface Modulate Phototoxicity of a Porphycene Anti-ICAM-1 Immunoconjugate; Therapeutic Implications.” Langmuir 29, no. 31 (August 6, 2013): 9734–9743.
Author's final manuscript