title: Optimal photosensitizers for photodynamic therapy of infections should kill bacteria but spare neutrophils.
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.
authors.affiliation: Department of Orthopedic Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Tanaka
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshihara
authors.forename: Nariyoshi
authors.initials: N
authors.lastname: Shinomiya
authors.forename: Shuhji
authors.initials: S
authors.lastname: Seki
authors.forename: Koichi
authors.initials: K
authors.lastname: Nemoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hirayama
authors.forename: Tianhong
authors.initials: T
authors.lastname: Dai
authors.forename: Liyi
authors.initials: L
authors.lastname: Huang
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morimoto
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D017319:Photosensitizing Agents / Q000494:pharmacology*
chemical_list: D017319:Photosensitizing Agents