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Photodynamic therapy induces selective extravasation of macromolecules: Insights using intravital microscopy

Paper ID Volume ID Publish Year Pages File Format Full-Text
30041 44456 2010 8 PDF Available
Title
Photodynamic therapy induces selective extravasation of macromolecules: Insights using intravital microscopy
Abstract

Photodynamic therapy (PDT) with Visudyne® acts by direct cellular phototoxicity and/or by an indirect vascular-mediated effect. Here, we demonstrate that the vessel integrity interruption by PDT can promote the extravasation of a macromolecular agent in normal tissue. To obtain extravasation in normal tissue PDT conditions were one order of magnitude more intensive than the ones in tissue containing neovessels reported in the literature.Fluorescein isothiocyanate dextran (FITC-D, 2000 kDa), a macromolecular agent, was intravenously injected 10 min before (LK0 group, n = 14) or 2 h (LK2 group, n = 16) after Visudyne®-mediated PDT in nude mice bearing a dorsal skin fold chamber. Control animals had no PDT (CTRL group, n = 8). The extravasation of FITC-D from blood vessels in striated muscle tissue was observed in both groups in real-time for up to 2500 s after injection. We also monitored PDT-induced leukocyte rolling in vivo and assessed, by histology, the corresponding inflammatory reaction score in the dorsal skin fold chambers.In all animals, at the applied PDT conditions, FITC-D extravasation was significantly enhanced in the PDT-treated areas as compared to the surrounding non-treated areas (p < 0.0001). There was no FITC-D leakage in the control animals. Animals from the LK0 group had significantly less FITC-D extravasation than those from the LK2 group (p = 0.0002). In the LK0 group FITC-D leakage correlated significantly with the inflammation (p < 0.001).At the selected conditions, Visudyne®-mediated PDT promotes vascular leakage and FITC-D extravasation into the interstitial space of normal tissue. The intensity of vascular leakage depends on the time interval between PDT and FITC-D injection. This concept could be used to locally modulate the delivery of macromolecules in vivo.

Keywords
Drug delivery; Photodynamic therapy; Visudyne®; Fluorescein isothiocyanate dextran; Dorsal skin fold chamber; Intravital microscopy
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Photodynamic therapy induces selective extravasation of macromolecules: Insights using intravital microscopy
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 98, Issue 1, 21 January 2010, Pages 69–76
Authors
, , , , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
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