Photosensitizer delivery to vulnerable atherosclerotic plaque: comparison of macrophage-targeted conjugate versus free chlorin(e6).

Abstract

We have previously shown that a conjugate (MA-ce6) between maleylated serum albumin and the photosensitizer chlorin(e6) (ce6) is targeted in vitro to macrophages via class A scavenger receptors. We now report on the ability of this conjugate to localize in macrophage-rich atherosclerotic plaques in vivo. Both the conjugate and the free photosensitizer ce6 are studied after injection into New Zealand White rabbits that are rendered atherosclerotic by a combination of aortic endothelial injury and cholesterol feeding into normal rabbits. Rabbits are sacrificed at 6 and 24 h after injection and intravascular fluorescence spectroscopy is carried out by fiber-based fluorimetry in intact blood-filled arteries. Surface spectrofluorimetry of numbered excised aortic segments together with injured and normal iliac arteries is carried out, and quantified ce6 content by subsequent extraction and quantitative fluorescence determination of the arterial segments and also of nontarget organs. There is good agreement between the various techniques for quantifying ce6 localization, and high contrast between arteries from atherosclerotic and normal rabbits is obtained. Fluorescence correlates with the highest burden of plaque in the aorta and the injured iliac artery. The highest accumulation in plaques is obtained using MA-ce6 at 24 h. Free ce6 gives better accumulation at 6 h compared to 24 h. The liver, spleen, lung, and gall bladder have the highest uptake in nontarget organs. Macrophage-targeted photosensitizer conjugates may have applications in both detecting and treating inflamed vulnerable plaque.

• Authors: Ahmed Tawakol, Ana P Castano, Florencia Anatelli, Gregory Bashian, Jeremy Stern, Touqir Zahra, Faten Gad, Stephanie Chirico, Atosa Ahmadi, Alan J Fischman, James E Muller, Michael R Hamblin
• Journal: Journal of biomedical optics (J Biomed Opt) 2006 Mar-Apr Vol. 11 Issue 2 Pg. 021008 ISSN: 1083-3668 [Print] United States
• PMID: 16674183 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Chlorophyllides
• Drug Combinations
• Photosensitizing Agents
• Porphyrins
• maleylalbumin
• Serum Albumin, Bovine
• phytochlorin

Topics

• Animals
• Atherosclerosis (drug therapy, metabolism, pathology)
• Carotid Stenosis (drug therapy, metabolism, pathology)
• Chlorophyllides
• Drug Combinations
• Drug Delivery Systems (methods)
• Macrophages (drug effects, metabolism, pathology)
• Male
• Metabolic Clearance Rate
• Organ Specificity
• Photochemotherapy (methods)
• Photosensitizing Agents (administration & dosage)
• Porphyrins (administration & dosage, pharmacokinetics)
• Rabbits
• Serum Albumin, Bovine (administration & dosage, pharmacokinetics)
• Tissue Distribution
• Treatment Outcome