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Amphiphilic tetracationic porphyrins are exceptionally active antimicrobial photosensitizers: In vitro and in vivo studies with the free‐base and Pd‐chelate
Author(s) -
Xuan Weijun,
Huang Liyi,
Wang Yuguang,
Hu Xiaoqing,
Szewczyk Grzegorz,
Huang YingYing,
ElHussein Ahmed,
Bommer Jerry C.,
Nelson Mark L.,
Sarna Tadeusz,
Hamblin Michael R.
Publication year - 2019
Publication title -
journal of biophotonics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.877
H-Index - 66
eISSN - 1864-0648
pISSN - 1864-063X
DOI - 10.1002/jbio.201800318
Subject(s) - antimicrobial , candida albicans , in vivo , singlet oxygen , chemistry , porphyrin , escherichia coli , staphylococcus aureus , microbiology and biotechnology , photosensitizer , hematoporphyrin , photodynamic therapy , in vitro , chelation , antibacterial activity , photochemistry , biology , biochemistry , organic chemistry , bacteria , oxygen , genetics , gene
Antimicrobial photodynamic inactivation (aPDI) employs the combination of nontoxic photosensitizing dyes and visible light to kill pathogenic microorganisms regardless of drug‐resistance, and can be used to treat localized infections. A meso‐substituted tetra‐methylpyridinium porphyrin with one methyl group replaced by a C12 alkyl chain (FS111) and its Pd‐derivative (FS111‐Pd) were synthesized and tested as broad‐spectrum antimicrobial photosensitizers when excited by blue light (5 or 10 J/cm 2 ). Both compounds showed unprecedented activity, with the superior FS111‐Pd giving 3 logs of killing at 1 nM, and eradication at 10 nM for Gram‐positive methicillin‐resistant Staphylococcus aureus . For the Gram‐negative Escherichia coli , both compounds produced eradication at 100 nM, while against the fungal yeast Candida albicans , both compounds produced eradication at 500 nM. Both compounds could be categorized as generators of singlet oxygen (Φ Δ = 0.62 for FS111 and 0.71 for FS111‐Pd). An in vivo study was carried out using a mouse model of localized infection in a partial thickness skin abrasion caused by bioluminescent Gram‐negative uropathogenic E. coli . Both compounds were effective in reducing bioluminescent signal in a dose‐dependent manner when excited by blue light (405 nm), but aPDI with FS111‐Pd was somewhat superior both during light and in preventing recurrence during the 6 days following PDT.