Topical photodynamic treatment with poly-l-lysine–chlorin p6 conjugate improves wound healing by reducing hyperinflammatory response in Pseudomonas aeruginosa-infected wounds of mice

Abstract

We report the results of our investigations on the effect of antimicrobial photodynamic treatment (APDT) with poly-lysine-conjugated chlorin p6 (pl-cp6) on proinflammatory cytokine expression and wound healing in a murine excisional wound model infected with Pseudomonas aeruginosa. Treatment of infected wounds with pl-cp6 and light doses of 60 and 120 J/cm(2) reduced the bacterial load by ~1.5 and 2.0 log, respectively, after 24 h. The treated wounds healed ~5 days earlier as compared to untreated control and wound closure was not dependent on light dose. Interestingly, at 96 h post-treatment, drug-treated wounds irradiated at 60 J/cm(2) showed considerable reduction of proinflammatory cytokines IL-6 (approximately five times) and TNF-α (approximately four times) compared to untreated control. Further, exposure of culture supernatants to similar light dose and pl-cp6 concentration under in vitro conditions reduced the protease activity by ~50 % as compared to the untreated control, suggesting inactivation of extracellular virulent factors. Additionally, histological analysis of treated infected wounds showed complete reepithelialization, ordered collagen fibers, and considerable decrease in inflammatory cell infiltration compared to untreated wounds. These results imply that pl-cp6-mediated PDT reduces hyperinflammatory response of infected wounds, leading to acceleration of wound healing.

Antibacterial photodynamic therapy: overview of a promising approach to fight antibiotic-resistant bacterial infections

“…Another recent clinical study reported that APDT of P. aeruginosa-caused skin ulcers in the lower limbs resulted in significant bactericidal outcome and wound healing-promoting effects [232]. This is in line with a previous study in mice, where APDT was shown to reduce the hyper-inflammatory response in P. aeruginosa-infected skin wounds [233]. Additionally, APDT is also used in the clinical management of diabetic foot, which causes sizeable infection-related complications in diabetic patients.…”

A clinical study of photodynamic therapy for chronic skin ulcers in lower limbs infected with Pseudomonas aeruginosa

“…Mills [18] proved MAL-PDT increases MMP-1, MMP-9 and TGF-b3 production during matrix remodelling, ultimately producing scars with improved dermal matrix architecture. Sahu's study [25] showed that photodynamic treatment of wounds with pl-cp6 not only kills the bacteria but also reduces hyper-inflammatory response of P. aeruginosa-infected wounds in mice, leading to acceleration of wound healing. Currently, however, no basic research has fully elucidated related mechanisms, which still await further in-depth studies.…”

“…e The skin ulcer surface was significantly cleaner and the size was reduced 3 days after the second PDT treatment Arch Dermatol Res anti-inflammatory, and healing-promoting effects [1]. Fourth, Several novel studies have demonstrated that PDT has positive effects on histological aspects of wound healing [18,23,25]. Mills [18] proved MAL-PDT increases MMP-1, MMP-9 and TGF-b3 production during matrix remodelling, ultimately producing scars with improved dermal matrix architecture.…”

Topical antimicrobial photodynamic therapy improves angiogenesis in wounds of diabetic mice

“…PDT, in addition to the antibacterial effect, has also been shown to have influence on several other factors like bacterial toxins [4], proinflammatory cytokines [5], matrix metalloproteases, collagen synthesis, and remodeling [6] in wounds. Therefore, APDT appears promising for the treatment of diabetic wounds where healing is impaired and the treatment is further complicated by bacterial infection [7][8][9].…”