The antibacterial activity of photodynamic agents against multidrug resistant bacteria causing wound infection

Antimicrobial photodynamic inactivation (aPDI) of multidrug-resistant (MDR) wound pathogens was evaluated with cationic porphyrin derivatives (CPDs). MDR bacterial strains including Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, and Klebsiella pneumoniae were used. The CPDs named PM, PE, PN, and PL were synthesized as a photosensitizer (PS). A diode laser with a wavelength of 655 nm was used as a light source. aPDI of the combinations formed with different energy densities (50, 100, and 150 J/cm²) and PS concentrations (ranging from 3.125 to 600 µM) were evaluated on each bacterial strain. Dark toxicity, cytotoxicity, and phototoxicity were determined on fibroblast cells. In the aPDI groups, survival reductions of up to 5.80 log₁₀ for E. coli, 5.90 log₁₀ for P. aeruginosa, 6.11 log₁₀ for K. pneumoniae, and 6.78 log₁₀ for A. baumannii were obtained. The cytotoxic effect of PL and PM on fibroblast cells was very limited. PN was the type of CPD with the highest dark toxicity on fibroblast cells. In terms of providing broad-spectrum aPDI without or with very limited cytotoxic effect, the best result was observed in aPDI application with PL. The other CPDs need some modifications to show bacterial selectivity for use at 50 µM and above.     

Conjugated Polythiophene/Porphyrin Complex for Rapid and Simple Detection of Bacteria in Drinking Water

An electrostatic complex combining anionic water‐soluble conjugated polythiophene (PTP) with commercial cationic porphyrin ([5,10,15,20‐tetrakis(4‐(trimethylammonio)‐phenyl)‐21H,23H‐porphine tetratosylate] (TMP)) has been designed for rapid and simple detection of bacteria infection in drinking water by applying fluorescence resonance energy transfer (FRET) strategy. There is efficient FRET from PTP to TMP for the electrostatic complex of PTP/TMP. Upon the addition of bacteria, the cationic TMP is adsorbed tightly to the negatively charged membrane surface of bacteria through electrostatic interactions, making the PTP reside in much farther proximity to TMP than that in the absence of bacteria. Therefore, much weaker FRET is observed. Interesting, the detection for bacteria based on FRET changes of PTP/TMP complex is visual in view of the color changes under ultraviolet (UV) irradiation. This assay takes advantage of the light‐harvesting property of conjugated polymer and the ratiometric measurements for minimizing the nonspecific binding effect. The strategy is promising in pathogen detection in drinking water and other sources.

     

AGET ATRP of Poly[poly(ethylene glycol) methyl ether methacrylate] Catalyzed by Hydrophobic Iron(III)–Porphyrins

Commercially available hydrophobic porphyrins are investigated as an environmentally friendly catalytic system for iron‐mediated atom transfer radical polymerization (ATRP) of poly(ethylene glycol) monomethyl ether methacrylate (PEGMA). Polymerizations in organic solvent are optimized using activators generated by electron transfer (AGET ATRP), based on iron(III)–porphyrin complexes, and tin(II) 2‐ethyl hexanoate or ascorbic acid as a reducing agent. Copper‐free PPEGMA macromolecules are obtained with high conversion, controlled molecular weight, and polydispersity index compared with standard copper‐based ATRP. The facile preparation and availability of the catalyst, together with its expected low toxicity, represent clear advantages for the synthesis of PPEGMA‐based materials for biomedical use.

     

Cellular Phototoxicity Evoked Through the Inhibition of Human ABC Transporter ABCG2 by Cyclin-dependent Kinase Inhibitors In vitro

PURPOSE: The physiological importance of the human ATP-binding cassette (ABC) transporter ABCG2 has been recognized with regard to porphyrin-mediated photosensitivity. Functional impairment owing to inhibition of ABCG2 by drugs or its genetic polymorphisms may lead to the disruption of porphyrin homeostasis, which in turn causes cellular toxicity. MATERIALS AND METHODS: We evaluated the impact on photosensitivity of the inhibition by cyclin-dependent kinase (CDK) inhibitors of ABCG2 function. For this purpose, we established new methods for photosensitivity assays by using Flp-In-293 cells and plasma membrane vesicles prepared from Sf9 insect cells. With the new methods, we subsequently tested CDK inhibitors, i.e., purvalanol A, WHI-P180, bohemine, roscovitine, and olomoucine. RESULTS: Among CDK inhibitors tested, purvalanol A was found to be the most potent inhibitor (IC50=3.5 microM) for ABCG2-mediated hematoporphyrin transport. At a concentration of 2.5 microM, it evoked the photosensitivity of ABCG2-expressing Flp-In-293 cells treated with pheophorbide a. WHI-P180 moderately inhibited ABCG2 function, exhibiting weak phototoxicity. In contrast, the phototoxicity of bohemine, roscovitine, and olomoucine were minimal in our assay system. CONCLUSIONS: It is suggested that the planar structure is an important factor for interactions with the active site of ABCG2. The present study provides a new approach to studying drug-induced phototoxicity in vitro.     

Development and applications of photo-triggered theranostic agents

Theranostics, the fusion of therapy and diagnostics for optimizing efficacy and safety of therapeutic regimes, is a growing field that is paving the way towards the goal of personalized medicine for the benefit of patients. The use of light as a remote-activation mechanism for drug delivery has received increased attention due to its advantages in highly specific spatial and temporal control of compound release. Photo-triggered theranostic constructs could facilitate an entirely new category of clinical solutions which permit early recognition of the disease by enhancing contrast in various imaging modalities followed by the tailored guidance of therapy. Finally, such theranostic agents could aid imaging modalities in monitoring response to therapy. This article reviews recent developments in the use of light-triggered theranostic agents for simultaneous imaging and photoactivation of therapeutic agents. Specifically, we discuss recent developments in the use of theranostic agents for photodynamic-, photothermal- or photo-triggered chemotherapy for several diseases.     

Flavin-dependent antioxidant properties of a new series of meso-N,N'-dialkyl-imidazolium substituted manganese(III) porphyrins

A number of synthetic manganese complexes exhibit both in vitro and in vivo catalytic antioxidant activities. This study reports that the antioxidant potencies of a new series of meso-N,N'-dialkyl-imidazolium substituted manganese(III) porphyrins are dependent, in part, on their ability to redox cycle with endogenous flavin-dependent oxidoreductases. Inhibition of lipid peroxidation activities of these novel cationic porphyrins was compared using rat brain homogenate as a source of lipids and endogenous oxidoreductases. Iron and ascorbate was used as initiators of lipid peroxidation, and two indices of lipid peroxidation (thiobarbituric acid reactive species (TBARS) and F(2)-isoprostanes) were determined. All meso-N,N'-dialkyl-imidazolium substituted porphyrins tested were potent inhibitors of lipid peroxidation with IC(50) ranging from 0.1 to 34 microM with a metal-dependent potency of Mn(III)>Co(III)>Zn(II). A flavin-dependent oxidoreductase antioxidant process was supported by the ability of the diphenyleneiodonium chloride (DPI, a flavoenzyme inhibitor) to decrease the potency of Mn-porphyrins in the lipid peroxidation model and that Mn-porphyrins stimulate NADPH oxidation in rat brain homogenates. These data suggest that metalloporphyrins may have differential antioxidant effects in tissues due to the presence or absence of flavin-dependent oxidoreductases.     

Efficient methods for the synthesis of 5‐(4‐[18F]fluorophenyl)‐10,15,20‐tris(3‐methoxyphenyl)porphyrin as a potential imaging agent for tumor

F‐18‐labeled porphyrins, the potential tracing and detecting agents for tumor have been synthesized and characterized by two convenient routes: one is a mixed aldehyde condensation, which involves acid‐catalyzed condensation of pyrrole, m‐anisaldehyde and 4‐[¹⁸F]fluorobenzaldehyde. The other is the acid‐catalyzed condensation of tetrapyrrane with 4‐[¹⁸F]fluorobenzaldehyde. The synthetic methodologies including solvents, reaction concentrations and catalysts are optimized for radiolabeled porphyrins. The methods also provide the desired product in reasonable radiochemical yield (20–26%) compared with those of cold chemical synthesis (1–3%) and with high radiochemical purity (>95%). The methods described here would be effective and convenient ways to produce radiolabeled porphyrin. Copyright © 2005 John Wiley & Sons, Ltd.     

An effect of erythrocyte protoporphyrin on blood manganese in lead-exposed children and adults

Summary In one study in 2- and 3-year-old children (geom. average 143 g Pb/1) and in two studies in workers (geom. average 483 pg Pb/1 and 323 g Pb/1) manganese in blood levels increased with blood lead and with free erythrocyte porphyrin (FEP). The zero-order correlation between PbB and MnB disappeared when FEP was kept constant. The conclusion is drawn that the increase of MnB with increasing PbB is probably not due to simultaneous exposure, neither to direct interaction between Pb and Mn, but mediated through a relationship between Mn and porphyrin in erythrocytes.This study was supported by a grant from the Dutch Prevention Fund     

含多个氧化还原中心的四(对-十二酰氧基)苯基卟啉钴的电化学行为

目的 合成并表征四（对－十二酰氧基）苯基卟啉钴（简称为：TLPPCo）。方法 用元素分析,紫外可见光谱,红外光声光谱,摩尔电导和核磁共振氢谱等方法表征TDPPCo的结构,用循环伏安法研究TLPPCo的电化学行为。结果 TLPPCo发生了三步氧化还原反应,每一步电极反应的半波电位及存在的物种是：[TLPPCo(Ⅲ)]^ /[TLPPCo(Ⅱ)]E1/2=-0.262V,[TLPPCo(Ⅱ)]/[TLPPCo(Ⅰ)]^-E1/2=-1.217V,[TLPPCo(Ⅰ)]^-/[TLPPCo(Ⅰ)]^2-E1/2=-1.662V。结论 TLPPCo可作为一种具有应用前景的催化剂。     

2,7,12,18-四甲基-3,8-二(1-烷氧乙基)-13,17-二(3-羟基丙基)卟啉衍生物的合成及其光敏活性

以氯化血红素为起始原料设计合成了６个全新的卟啉衍生物．在Ｄ２Ｏ中对ＮＡＤＰＨ光氧化作用的敏化效应实验表明，所合成的目标化合物均具有光敏活性，其中３，８位含甲氧基、乙氧基、正丙氧基、异丙氧基的卟啉化合物活性明显高于参比药物ＨｐＤ，可望替代ＨｐＤ用于肿瘤的光动力治疗，值得进一步深入研究．