An effective zinc phthalocyanine derivative against multidrug-resistant bacterial infection

Abstract

Bacterial skin and soft tissue infections are abundant worldwide. The rise in the incidence of multidrug-resistant (MDR) bacterial infections has made the need for alternative means of treatment more pressing. We herein report a zinc phthalocyanine derivative, pentalysine [Formula: see text]-carbonylphthalocyanine zinc (ZnPc-(Lys)[Formula: see text] and its strong capability of killing nosocomial MDR bacteria, including MDR-Escherichia coli and MDR-Acinetobacter baumannii. In vitro studies, we observed that ZnPc-(Lys)5 in micromolar concentrations killed above MDR bacteria in 6~6.5 log10 orders with only 5-min illumination of red light at a dosage of 12.75 J/cm[Formula: see text]. Further in vivo studies on a mouse infection model demonstrated that ZnPc-(Lys)5 efficiently inhibited the MDR bacterial growth after one-time photodynamic antibacterial therapy and, interestingly, significantly accelerated the wound healing. Putting together, our findings establish ZnPc-(Lys)5 as a potent antimicrobial candidate for the clinical test on localized infection.

The Role of Porphyrinoid Photosensitizers for Skin Wound Healing

“…Althoug authors were a bit cautious due to the limited population tested and the lack of a co Considering the high efficacy of the zinc complex of pentalysine β-carbonylphthalocyanine [ZnPc-(Lys) 5 ] (Scheme 1) to photoinactivate in vitro nosocomial MDR bacteria, such as MDR-E. coli (MREC) and MDR-A. baumannii (MRAB) under red light, Wang and coworkers considered its use to treat in vivo infected wounds in mice [130]. The strategy to prepare this PS was previously reported by the authors and involved the coupling of the unsymmetrical Pc ZnPc-COOH with pentalysine in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) (Scheme 1) [131].…”

“…The higher PS concentration required for the in vivo studies was justified by PS with nonspecific binding to the wound tissue instead of selective absorption by bacteria and by the occurrence of some photobleaching caused by the higher light dose required for an efficient in vivo treatment. [130] with permission from World Scientific Publishing Co., Inc., Singapore).…”

“…Reduction. (A) Multidrug-resistant E. coli (MREC) and (B) multidrug-resistant A. baumannii (MRAB) in infected incision wounds on mice upon aPDT treatment with ZnPc-(Lys) 5 ; effects of ZnPc-(Lys) 5 concentration on the aPDT healing of (C) MREC and (D) MRAB (figure adapted from[130] with permission from World Scientific Publishing Co., Inc., Singapore).…”

Household light source for potent photo-dynamic antimicrobial effect and wound healing in an infective animal model

“…The results demonstrated that at a concentration of 2 µM, ZnPc(Lys) 5 remarkably eradicated both MDR strains in vitro under a light fluence (12.7 J/cm 2 and 25 J/cm 2 ). PACT effect was further seen on an animal model of the MDR strain at a concentration (0.1 mM or 0.5 mM), demonstrating a high antibacterial efficacy in localized infected animal model [19]. The present work aims to study the effect of light fluence on bacterial killing using PS pentalysine-β-carbonylphthalocyanine zinc, ZnPc(Lys) 5 .…”

Antimicrobial photodynamic therapy against Staphylococcus aureus using zinc phthalocyanine and zinc phthalocyanine-integrated TiO2 nanoparticles

“…Features of ZnPcs such as solubility in water/ lipid and ionization constant [16,18,26] are also important for photoinactivation on the cell. Studies in recent years indicate that ZnPcs can be functionalized as efficient PS agents against Gram-positive and Gram-negative bacteria [27][28][29][30][31][32][33][34]. Also, antimicrobial efficiency of ZnPcs has been tested as in vivo animal models for clinical trials [35,36].…”