Document Detail


Real-time fluorescence monitoring of phenothiazinium photosensitizers and their anti-mycobacterial photodynamic activity against Mycobacterium bovis BCG in in vitro and in vivo models of localized infection.
MedLine Citation:
PMID:  17914486     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An objective was to explore the photodynamic activity of two cationic photosensitizers (PS) (benzo[a]phenothiazinium chloride and benzo[a]phenoselenazinium chloride) against Mycobacterium bovis BCG both in vitro and in a murine model of BCG-granuloma. The hypothesis being tested in this study was that cationic molecules could best interact with the negatively charged membrane of BCG as a model for mycobacterial infection. Cells in culture were incubated with various concentrations of PS and subsequently illuminated using a 635 nm diode laser. Dark- and light-induced killing profiles were generated as a function of fluence and dye concentration. In vivo, local injection of the PS into subcutaneous Mycobacterium-induced granuloma sites in murine model was followed by red light illumination of the same area. A special microscope was fabricated for real-time in vivo fluorescent microscopy to monitor EtNBS delivery to subcutaneous murine granulomata. Both PS demonstrated good in vitro antimycobacterial photodynamic activity with varying degrees of toxicity under dark conditions. Real time in vivo monitoring of benzophenothiazine chloride in the mouse model indicated that this fluorescent photosensitizer was delivered rapidly to the subcutaneous granuloma site. In vivo, photosensitizer specific dark- and photo-toxicities depended on the structure, concentration of the photosensitizer and the light dose utilized. Cationic phenothiazine photosensitizers are promising candidates for use in anti-mycobacterial PDT for localized diseases such as cutaneous and pulmonary granulomata.
Authors:
Katie O'Riordan; Oleg E Akilov; Sung K Chang; James W Foley; Tayyaba Hasan
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-08-16
Journal Detail:
Title:  Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology     Volume:  6     ISSN:  1474-905X     ISO Abbreviation:  Photochem. Photobiol. Sci.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-04     Completed Date:  2008-01-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101124451     Medline TA:  Photochem Photobiol Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  1117-23     Citation Subset:  IM    
Affiliation:
Wellman Centre for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, Boston, MA 02114, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Fluorescence
Granuloma / drug therapy,  microbiology*
Mice
Mice, Inbred BALB C
Microscopy, Fluorescence / methods*
Mycobacterium bovis / drug effects*
Organoselenium Compounds / pharmacology*,  therapeutic use
Photochemotherapy
Photosensitizing Agents / pharmacology*,  therapeutic use
Thiazines / pharmacology*,  therapeutic use
Tuberculosis / drug therapy*,  microbiology
Chemical
Reg. No./Substance:
0/Organoselenium Compounds; 0/Photosensitizing Agents; 0/Thiazines; 136825-96-2/5-ethylamino-9-diethylaminobenzo(a)phenothiazinium; 136825-97-3/5- ethylamino-9-diethylaminobenzo(a)phenoselenazinium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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