Potential of hydrogen (pH) is one of the most relevant parameters characterizing aqueous solutions. In biology, pH is intrinsically linked to cellular life since all metabolic pathways are implicated into ionic flows. In that way, determination of local pH offers a unique and major opportunity to increase our understanding of biological systems. Whereas the most common technique to obtain these data in analytical chemistry is to directly measure potential between two electrodes, in biological systems, this information has to be recovered in-situ without any physical interaction. Based on their non-invasive optical properties, fluorescent pH-sensitive probe are pertinent tools to develop. One of the most notorious pH-sensitive probes is fluorescein. In addition to excellent photophysical properties, this fluorophore presents a pH-sensitivity around neutral and physiologic domains. This review intends to shed new light on the recent use of fluorescein as pH-sensitive probes for biological applications, including targeted probes for specific imaging, flexible monitoring of bacterial growth, and biomedical applications.
Despite advances achieved over the last decade, infections caused by multi-drug-resistant bacterial strains are increasingly becoming important societal issues that need to be addressed. New approaches have already been developed in order to overcome this problem. Photodynamic antimicrobial chemotherapy (PACT) could provide an alternative to fight infectious bacteria. Many studies have highlighted the value of cationic photosensitizers in order to improve this approach. This study reports the synthesis and the characterization of cationic porphyrins derived from methylimidazolium and phenylimidazolium porphyrins, along with a comparison of their photophysical properties with the well-known N-methylpyridyl (pyridinium) porphyrin family. PACT tests conducted with the tetracationic porphyrins of these three families showed that these new photosensitizers may offer a good alternative to the classical pyridinium porphyrins, especially against S.aureus and E.coli. In addition, they pave the way to new cationic photosensitizers by the means of derivatization through amide bond formation.
Establishing the rapid and accurate diagnosis of sepsis is a key component to the improvement of clinical outcomes. The ability of analytical platforms to rapidly detect pathogen-associated molecular patterns (PAMP) in blood could provide a powerful host-independent biomarker of sepsis. A novel concept was investigated based on the idea that a pre-bound and fluorescent ligand could be released from lectins in contact with high-affinity ligands (such as PAMPs). To create fluorescent ligands with precise avidity, the kinetically followed TEMPO oxidation of yeast mannan and carbodiimide coupling were used. The chemical modifications led to decreases in avidity between mannan and human collectins, such as the mannan-binding lectin (MBL) and human surfactant protein D (SP-D), but not in porcine SP-D. Despite this effect, these fluorescent derivatives were captured by human lectins using highly concentrated solutions. The resulting fluorescent beads were exposed to different solutions, and the results showed that displacements occur in contact with higher affinity ligands, proving that two-stage competition processes can occur in collectin carbohydrate recognition mechanisms. Moreover, the fluorescence loss depends on the discrepancy between the respective avidities of the recognized ligand and the fluorescent mannan. Chemically modulated fluorescent ligands associated with a diversity of collectins may lead to the creation of diagnostic tools suitable for multiplex array assays and the identification of high-avidity ligands.
L’émergence de nouvelles souches bactériennes résistantes a signé la fin de l’« âge d’or » des antibiotiques. L’organisation mondiale de la santé a reconnu l’imminence des problèmes associés à ces nouvelles bactéries, qui engendrent de nouveau une mortalité en augmentation. Afin de palier à ce problème, de nouvelles alternatives aux antibiotiques sont envisagées par les chercheurs à travers le monde. La thérapie photodynamique antimicrobienne est l’une de ces alternatives. Elle a su se démarquer grâce à son incapacité à induire la résistance bactérienne. Alors que les résultats furent initialement très prometteurs contre les bactéries Gram positif, une moins bonne sensibilité fut rapidement observée de la part des bactéries Gram négatif. Afin d’augmenter le potentiel antibactérien de cette technique, diverses stratégies furent élaborées comme l’utilisation de photosensibilisateurs cationiques, l’ajout d’un agent de ciblage, ou la présence d’un agent de perméabilisation membranaire. L’un de ces agents est la polymyxine B, un peptide antimicrobien qui arbore une très bonne affinité avec les bactéries Gram négatif. Dans cette étude, nous avons voulu associer chimiquement différents photosensibilisateurs avec des dérivés de polymyxines B de façon covalente, par l’intermédiaire d’un bras « spacer » ou d’une plateforme. L’association de ces deux familles de molécules a permis d’élaborer de nouveaux composés qui ont démontré une activité photobactéricide accrue contre un large spectre de bactérie. De plus, ces composés ont montré une affinité augmentée pour les bactéries, ce qui permettra de réduire les effets secondaires sur les cellules humaines. Cette étude confirme l’importance d’utiliser des peptides antimicrobiens afin d’améliorer la thérapie photodynamique. Ces travaux seront approfondis afin de permettre la création de nouveaux traitements dermatologiques basées sur cette nouvelle thérapie et efficaces contre un large spectre de souche bactérienne
1 February 2024 in Photochemical & Photobiological Sciences