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 (MRSA), and morphological alteration and viability of neutrophils were studied. Most neutrophils were viable (> 80%) after PDT using toluidine blue-O or methylene blue, 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 toluidine blue-O or methylene blue can preserve host neutrophils while exerting a significant therapeutic effect on in vivo localized microbial infection.

Novel Broad-Spectrum Antimicrobial Photoinactivation of In Situ Oral Biofilms by Visible Light plus Water-Filtered Infrared A

“…On the other hand, the hydrophilic TB exhibits limited diffusion into the double-layered phospholipid membrane of the mammalian cells, resulting in low cytocidal effects on host cells, as highlighted in several previous studies (62,63). This is an encouraging fact for the future clinical application of this photosensitizer (64).…”

In vitro photoinactivation of bovine mastitis related pathogens

“…Although few studies have focused on the potential effects of PDT with phenothiazinium dyes on healthy cells or the immune system, some studies have investigated the action of PDT on fibroblasts, keratinocytes, or neutrophils [45][46][47]. Tanaka et al [47] In conventional treatment of bovine mastitis, topical antibiotic is applied through the teat canal of the mammary gland after milking. For this reason, we believe that for PDT clinical trials, PS should be administered after milking, as well as a conventional treatment.…”

Photodynamic Antimicrobial Chemotherapy (PACT) in osteomyelitis induced by Staphylococcus aureus: Microbiological and histological study

“…However, factors such as the pharmacokinetics of the PS, the use of an adequate wavelength and both irradiation and incubation protocols may affect the outcome of the procedure. The protocol used in the present study is clinically promising and this is probably one of the first reports on the effective use of direct topical application of PACT using TBO in infected bone.A study of cytotoxicity of PACT on neutrophils [27] concluded that the use of this therapy may preserve the viability of the cells helping in the control of the infection. An important finding from the present study is that, the group treated with PACT presented predominantly absence of acute inflammation, typical phase in which neutrophils are present.…”