ROS generating BODIPY loaded nanoparticles for photodynamic eradication of biofilms

Bacterial biofilms can pose a serious health risk to humans and are less susceptible to antibiotics and disinfection than planktonic bacteria. Here, a novel method for biofilm eradication based on antimicrobial photodynamic therapy utilizing a nanoparticle in conjunction with a BODIPY derivative as photosensitizer was developed. Reactive oxygen species are generated upon illumination with visible light and lead to a strong, controllable and persistent eradication of both planktonic bacteria and biofilms. One of the biggest challenges in biofilm eradication is the penetration of the antimicrobial agent into the biofilm and its matrix. A biocompatible hydrophilic nanoparticle was utilized as a delivery system for the hydrophobic BODIPY dye and enabled its accumulation within the biofilm. This key feature of delivering the antimicrobial agent to the site of action where it is activated resulted in effective eradication of all tested biofilms. Here, 3 bacterial species that commonly form clinically relevant pathogenic biofilms were selected: Escherichia coli, Staphylococcus aureus and Streptococcus mutans. The development of this antimicrobial photodynamic therapy tool for biofilm eradication takes a promising step towards new methods for the much needed treatment of pathogenic biofilms

Development of Optical Ratiometric Nanosensor Systems

Optische Sonden für die Bildgebung auf Grundlage des pH-Wertes sind für die Wissenschaft von großem Interesse, da es sich beim pH-Wert um eine entscheidende Kenngröße für viele Prozesse in der Biotechnologie, Biologie, medizinische Diagnostik, biomedizinische Forschung und Materialkorrosion handelt. Optische pH-Sensoren, deren Funktionsprinzip auf dem photophysikalischen Prozess Fluoreszenz basieren, sind dabei von besonderem Interesse, da die Fluoreszenz eine sehr hohe Empfindlichkeit, welche sogar die Auflösung einzelner Moleküle ermöglicht, bietet. Dies ermöglicht den Einsatz von molekularen über nanoskaligen Sensorformaten bis hin zur Anwendung in planaren Optoden oder faseroptischen Sensoren, und gilt, neben der nicht-invasiven, zerstörungsfreien und kontaktlosen Natur optischer Fluoreszenzmessungen, als anwendungsfreundliche Eigenschaft dieser optischen Sensoren. Der Informationsgehalt fluoreszenzintensität-basierender Sensoren ist normalerweise unspezifisch auf die An- oder Abwesenheit des Fluorophors und des Analyten beschränkt. Weiterhin kann er durch Schwankungen der Intensität des Anregungslichts und Änderungen der Fluorophorkonzentration, z.B. durch Photodegradation, beeinflusst werden. Daher werden Fluoreszenzsensoren oftmals in referenzierten Systemen verwendet. Diese Systeme ermöglichen, durch die Einführung einer analyt-inerten Referenz, ein duales, ratiometrisches Auslesen der Fluoreszenzintensitäten von zwei spektral unterscheidbaren Komponenten. In dieser Arbeit wird das konzeptionelle Design einer modular variierbaren, auf mehreren Komponenten basierenden Plattform für die ratiometrische optische Analytmessung vorgestellt. Dazu wurden fluoreszente, leicht zugängliche und analyt-sensitive Boron-Dipyrromethene (BODIPYs) mit durch nahes Infrarot (NIR) anregbare, mehrfarbig emittierende Aufkonvertierungs-Nanopartikel (UCNPs) kombiniert. Das Sensorprizip beruht dabei auf einem inneren Filter-Effekt der spektral abgestimmten Komponenten.Optical probes for monitoring, imaging, and sensing of pH are of great interest for the scientific community as pH is a crucial marker for many processes in biotechnology, biology, medical diagnostics, biomedical research, and material corrosion. Thereby, optical pH sensors based on fluorescence have attracted interest in particular as fluorescence offers a high sensitivity down to the single molecule level, can be read out with relatively simple and readily miniaturized instrumentation, and allows online in situ measurements. Also the versatility ranging from molecular and nanosensor formats to planar optodes and fiber-optic sensors, and the non-invasive, non-destructive, and contactless nature of the measurement are application-friendly features. The information content, which is offered by a fluorescence intensity-based sensor, is usually unspecific and limited on the presence or the absence of the chromophore or analyte and can additionally be hampered by fluctuation of the excitation light intensity and changes in fluorophore concentration, e.g., due to photobleaching. Therefore, many fluorescence sensors are utilized in referenced systems, which enable twowavelength ratiometric measurements of the fluorescence intensity by the introduction of an analyte-inert reference with a spectrally distinguishable emission. This work presents the rational design of a versatile, modular, multi-component-based platform for ratiometric optical analyte sensing that can be simply adapted to different formats and measurement geometries. Therefore, readily available analyte-responsive fluorescent boron-dipyrromethene (BODIPY) dyes and near infrared (NIR)-excitable multicolouremissive upconversion nanoparticles (UCNPs) were combined utilizing an inner filter-based strategy with spectrally matched moieties

Development of Optical Ratiometric Nanosensor Systems

Optische Sonden für die Bildgebung auf Grundlage des pH-Wertes sind für die Wissenschaft von großem Interesse, da es sich beim pH-Wert um eine entscheidende Kenngröße für viele Prozesse in der Biotechnologie, Biologie, medizinische Diagnostik, biomedizinische Forschung und Materialkorrosion handelt. Optische pH-Sensoren, deren Funktionsprinzip auf dem photophysikalischen Prozess Fluoreszenz basieren, sind dabei von besonderem Interesse, da die Fluoreszenz eine sehr hohe Empfindlichkeit, welche sogar die Auflösung einzelner Moleküle ermöglicht, bietet. Dies ermöglicht den Einsatz von molekularen über nanoskaligen Sensorformaten bis hin zur Anwendung in planaren Optoden oder faseroptischen Sensoren, und gilt, neben der nicht-invasiven, zerstörungsfreien und kontaktlosen Natur optischer Fluoreszenzmessungen, als anwendungsfreundliche Eigenschaft dieser optischen Sensoren. Der Informationsgehalt fluoreszenzintensität-basierender Sensoren ist normalerweise unspezifisch auf die An- oder Abwesenheit des Fluorophors und des Analyten beschränkt. Weiterhin kann er durch Schwankungen der Intensität des Anregungslichts und Änderungen der Fluorophorkonzentration, z.B. durch Photodegradation, beeinflusst werden. Daher werden Fluoreszenzsensoren oftmals in referenzierten Systemen verwendet. Diese Systeme ermöglichen, durch die Einführung einer analyt-inerten Referenz, ein duales, ratiometrisches Auslesen der Fluoreszenzintensitäten von zwei spektral unterscheidbaren Komponenten. In dieser Arbeit wird das konzeptionelle Design einer modular variierbaren, auf mehreren Komponenten basierenden Plattform für die ratiometrische optische Analytmessung vorgestellt. Dazu wurden fluoreszente, leicht zugängliche und analyt-sensitive Boron-Dipyrromethene (BODIPYs) mit durch nahes Infrarot (NIR) anregbare, mehrfarbig emittierende Aufkonvertierungs-Nanopartikel (UCNPs) kombiniert. Das Sensorprizip beruht dabei auf einem inneren Filter-Effekt der spektral abgestimmten Komponenten.Optical probes for monitoring, imaging, and sensing of pH are of great interest for the scientific community as pH is a crucial marker for many processes in biotechnology, biology, medical diagnostics, biomedical research, and material corrosion. Thereby, optical pH sensors based on fluorescence have attracted interest in particular as fluorescence offers a high sensitivity down to the single molecule level, can be read out with relatively simple and readily miniaturized instrumentation, and allows online in situ measurements. Also the versatility ranging from molecular and nanosensor formats to planar optodes and fiber-optic sensors, and the non-invasive, non-destructive, and contactless nature of the measurement are application-friendly features. The information content, which is offered by a fluorescence intensity-based sensor, is usually unspecific and limited on the presence or the absence of the chromophore or analyte and can additionally be hampered by fluctuation of the excitation light intensity and changes in fluorophore concentration, e.g., due to photobleaching. Therefore, many fluorescence sensors are utilized in referenced systems, which enable twowavelength ratiometric measurements of the fluorescence intensity by the introduction of an analyte-inert reference with a spectrally distinguishable emission. This work presents the rational design of a versatile, modular, multi-component-based platform for ratiometric optical analyte sensing that can be simply adapted to different formats and measurement geometries. Therefore, readily available analyte-responsive fluorescent boron-dipyrromethene (BODIPY) dyes and near infrared (NIR)-excitable multicolouremissive upconversion nanoparticles (UCNPs) were combined utilizing an inner filter-based strategy with spectrally matched moieties

Discrete multiporphyrin pseudorotaxane assemblies from di- and tetravalent porphyrin building blocks

Two pairs of divalent and tetravalent porphyrin building blocks carrying the complementary supramolecular crown ether/secondary ammonium ion binding motif have been synthesized and their derived pseudorotaxanes have been studied by a combination of NMR spectroscopy in solution and ESI mass spectrometry in the gas phase. By simple mixing of the components the formation of discrete dimeric and trimeric (metallo)porphyrin complexes predominates, in accordance to binding stoichiometry, while the amount of alternative structures can be neglected. Our results illustrate the power of multivalency to program the multicomponent self-assembly of specific entities into discrete functional nanostructures

Dynamic Parameters of Hypothermic Machine Perfusion—An Image of Initial Graft Function in Adult Kidney Transplantation?

Kidney allografts are subjected to ischemia reperfusion injury during the process of transplantation. Hypothermic machine perfusion (HMP) of deceased donor kidneys from organ procurement until transplantation is associated with a superior outcome when compared to static cold storage (SCS). Nevertheless, cold ischemia time (CIT) remains an independent risk factor for delayed graft function (DGF) in HMP-preserved kidney allografts as well. We performed a retrospective single-center study including all adult recipients who underwent deceased donor kidney-only transplantation at our center between January 2019 and December 2020. Beside the clinicopathological donor and recipient data, flow and resistance data during HMP were assessed. Short- and long-term kidney allograft outcome after end-ischemic HMP and SCS were analyzed and compared. Organ preservation consisted of either SCS (n = 88) or HMP (n = 45). There were no differences in recipient demographics and donor details between groups. CIT was significantly longer in the HMP group (16.5 [8.5–28.5] vs. 11.3 [5.4–24.1], p p = 0.0256; organ resistance 123.33 [57.67–165.50] vs. 51.33 [28.17–111.50] mmHg/mL/min, p = 0.0050). Recipients with DGF had significantly worse creatinine levels at discharge (2.54 [1.08–7.64] vs. 1.67 [0.90–6.56], p p = 0.0105). In conclusion, baseline HMP parameters could be applied as a predictive tool for initial graft function, which in turn determines long-term outcome

Data_Sheet_1_ROS generating BODIPY loaded nanoparticles for photodynamic eradication of biofilms.docx

Bacterial biofilms can pose a serious health risk to humans and are less susceptible to antibiotics and disinfection than planktonic bacteria. Here, a novel method for biofilm eradication based on antimicrobial photodynamic therapy utilizing a nanoparticle in conjunction with a BODIPY derivative as photosensitizer was developed. Reactive oxygen species are generated upon illumination with visible light and lead to a strong, controllable and persistent eradication of both planktonic bacteria and biofilms. One of the biggest challenges in biofilm eradication is the penetration of the antimicrobial agent into the biofilm and its matrix. A biocompatible hydrophilic nanoparticle was utilized as a delivery system for the hydrophobic BODIPY dye and enabled its accumulation within the biofilm. This key feature of delivering the antimicrobial agent to the site of action where it is activated resulted in effective eradication of all tested biofilms. Here, 3 bacterial species that commonly form clinically relevant pathogenic biofilms were selected: Escherichia coli, Staphylococcus aureus and Streptococcus mutans. The development of this antimicrobial photodynamic therapy tool for biofilm eradication takes a promising step towards new methods for the much needed treatment of pathogenic biofilms.</p

Data_Sheet_1_ROS generating BODIPY loaded nanoparticles for photodynamic eradication of biofilms.pdf

Bacterial biofilms can pose a serious health risk to humans and are less susceptible to antibiotics and disinfection than planktonic bacteria. Here, a novel method for biofilm eradication based on antimicrobial photodynamic therapy utilizing a nanoparticle in conjunction with a BODIPY derivative as photosensitizer was developed. Reactive oxygen species are generated upon illumination with visible light and lead to a strong, controllable and persistent eradication of both planktonic bacteria and biofilms. One of the biggest challenges in biofilm eradication is the penetration of the antimicrobial agent into the biofilm and its matrix. A biocompatible hydrophilic nanoparticle was utilized as a delivery system for the hydrophobic BODIPY dye and enabled its accumulation within the biofilm. This key feature of delivering the antimicrobial agent to the site of action where it is activated resulted in effective eradication of all tested biofilms. Here, 3 bacterial species that commonly form clinically relevant pathogenic biofilms were selected: Escherichia coli, Staphylococcus aureus and Streptococcus mutans. The development of this antimicrobial photodynamic therapy tool for biofilm eradication takes a promising step towards new methods for the much needed treatment of pathogenic biofilms.</p