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Optimal Photosensitizers for Photodynamic Therapy of Infections Should Kill Bacteria but Spare Neutrophils

Authors

  • Masamitsu Tanaka,

    1. Department of Orthopedic Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
    2. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA
    3. Department of Dermatology, Harvard Medical School, Boston, MA
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  • Manabu Kinoshita,

    1. Department of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Saitama, Japan
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  • Yasuo Yoshihara,

    1. Department of Orthopedic Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
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  • Nariyoshi Shinomiya,

    1. Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan
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  • Shuhji Seki,

    1. Department of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Saitama, Japan
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  • Koichi Nemoto,

    1. Department of Orthopedic Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
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  • Takahiro Hirayama,

    1. Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan
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  • Tianhong Dai,

    1. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA
    2. Department of Dermatology, Harvard Medical School, Boston, MA
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  • Liyi Huang,

    1. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA
    2. Department of Dermatology, Harvard Medical School, Boston, MA
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  • Michael R. Hamblin,

    1. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA
    2. Department of Dermatology, Harvard Medical School, Boston, MA
    3. Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA
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  • Yuji Morimoto

    Corresponding author
    1. Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan
      Corresponding author emails: dr21046@ndmc.ac.jp; moyan@ndmac.ac.jp (Yuji Morimoto)
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Corresponding author emails: dr21046@ndmc.ac.jp; moyan@ndmac.ac.jp (Yuji Morimoto)

Abstract

Photodynamic therapy (PDT) for localized microbial infections exerts its therapeutic effect both by direct bacterial killing and also by the bactericidal effects of host neutrophils stimulated by PDT. Therefore, PDT-induced damage to neutrophils must be minimized, while direct photoinactivation of bacteria is maintained to maximize the therapeutic efficacy of antimicrobial PDT in vivo. However, there has been no study in which the cytocidal effect of PDT on neutrophils was investigated. In this study, the cytocidal effects of PDT on neutrophils were evaluated using different antimicrobial photosensitizers to find suitable candidate photosensitizers for antimicrobial PDT. PDT on murine peripheral-blood neutrophils was performed in vitro using each photosensitizer at a concentration that exerted a maximum bactericidal effect on methicillin-resistant Staphylococcus aureus, and morphological alteration and viability of neutrophils were studied. Most neutrophils were viable (>80%) after PDT using toluidine blue-O (TB) or methylene blue (MB), while neutrophils showed morphological change and their viabilities were decreased (<70%) after PDT using other photosensitizers (erythrosine B, rose bengal, crystal violet, Photofrin, new methylene blue and Laserphyrin). These results suggest that PDT using TB or MB can preserve host neutrophils while exerting a significant therapeutic effect on in vivo localized microbial infection.

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