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Proceedings Paper

Beta-lactamase targeted enzyme activatable photosensitizers for antimicrobial PDT
Author(s): Xiang Zheng; Sarika Verma; Ulysses W. Sallum; Tayyaba Hasan
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Paper Abstract

Photodynamic therapy (PDT) as a treatment modality for infectious disease has shown promise. However, most of the antimicrobial photosensitizers (PS) non-preferentially accumulate in both bacteria and host tissues, causing host tissue phototoxicity during treatment. We have developed a new antimicrobial PDT strategy which exploits beta-lactam resistance mechanism, one of the major drug-resistance bacteria evolved, to achieve enhanced target specificity with limited host damage. Our strategy comprises a prodrug construct with a PS and a quencher linked by beta-lactam ring, resulting in a diminished phototoxicity. This construct, beta-lactamase enzyme-activated-photosensitizer (beta-LEAP), can only be activated in the presence of both light and bacteria, and remains inactive elsewhere such as mammalian tissue. Beta-LEAP construct had shown specific cleavage by purified beta-lactamase and by beta-lactamase over-expressing methicillin resistant Staphylococcus aureus (MRSA). Specific photodynamic toxicity was observed towards MRSA, while dark and light toxicity were equivalent to reference strains. The prodrug design, synthesis and photophysical properties will be discussed.

Paper Details

Date Published: 13 July 2009
PDF: 8 pages
Proc. SPIE 7380, Photodynamic Therapy: Back to the Future, 73802H (13 July 2009); doi: 10.1117/12.824500
Show Author Affiliations
Xiang Zheng, Wellman Ctr. for Photomedicine, MGH (United States)
Harvard Medical School (United States)
Sarika Verma, Wellman Ctr. for Photomedicine, MGH (United States)
Harvard Medical School (United States)
Ulysses W. Sallum, Wellman Ctr. for Photomedicine, MGH (United States)
Harvard Medical School (United States)
Tayyaba Hasan, Wellman Ctr. for Photomedicine, MGH (United States)
Harvard Medical School (United States)


Published in SPIE Proceedings Vol. 7380:
Photodynamic Therapy: Back to the Future

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