Search

Photoredox catalysis has emerged as a robust tool for chemical synthesis. However, it remains challenging to implement photoredox catalysis under physiological conditions due to the complex microenvironment and the quenching of photocatalyst by biologically relevant molecules such as oxygen. Here, we report that UV-absorbing N,N'-dinitroso-1,4-phenylenediamine derivatives can be selectively activated by fac-Ir(ppy) 3 photocatalyst within micellar nanoparticles under visible light irradiation (e.g., 500 nm) through photoredox catalysis in aerated aqueous solutions to form quinonediimine (QDI) residues with concomitant release of NO. Notably, the formation of QDI derivatives can actively scavenge the reactive oxygen species generated by fac-Ir(ppy) 3 , thus avoiding oxygen quenching of the photocatalyst. Further, we exemplify that the oxygen-tolerant photoredox catalysis-mediated NO release can not only kill planktonic bacteria in vitro but also efficiently treat MRSA infections in vivo., (© 2022 Wiley-VCH GmbH.)

Nitric oxide (NO) serves as a key regulator of many physiological processes and as a potent therapeutic agent. The local delivery of NO is important to achieve target therapeutic outcomes due to the toxicity of NO at high concentrations. Although light stimulus represents a non-invasive tool with spatiotemporal precision to mediate NO release, many photoresponsive NO-releasing molecules can only respond to ultraviolet (UV) or near-UV visible light with low penetration and high phototoxicity. We report that coumarin-based NO donors with maximal absorbances at 328 nm can be activated under (deep) red-light (630 or 700 nm) irradiation in the presence of palladium(II) tetraphenyltetrabenzoporphyrin, enabling stoichiometric and self-reporting NO release with a photolysis quantum yield of 8 % via photoredox catalysis. This NO-releasing platform with ciprofloxacin loading can eradicate Pseudomonas aeruginosa biofilm in vitro and treat cutaneous abscesses in vivo., (© 2021 Wiley-VCH GmbH.)

The development of new antibacterial agents that can efficiently eradicate biofilms is of crucial importance to combat persistent and chronic bacterial infections. Herein, the fabrication of photoresponsive vesicles capable of the sequential release of nitric oxide (NO) and gentamicin sulfate (GS) is reported, which can not only efficiently disperse Pseudomonas aeruginosa (P. aeruginosa) PAO1 biofilm but also kill the planktonic bacteria. Well-defined amphiphilic diblockcopolymers of poly(ethylene oxide)-b-poly(4-((2-nitrobenzyl)(nitroso)amino)benzyl methacrylate) (PNO) is first synthesized through atom transfer radical polymerization (ATRP). The PNO diblock copolymer self-assembled into vesicles in aqueous solution, and a hydrophilic antibiotic of GS is subsequently encapsulated into the aqueous lumens of vesicles. The vesicles undergo visible light-mediated N-NO cleavage, releasing NO and disintegrating the vesicles with the release of the GS payload. The sequential release of NO and GS efficiently eradicate P. aeruginosa PAO1 biofilm and kill the liberated bacteria, showing a better antibiofilm effect than that of NO or GS alone., (© 2021 Wiley-VCH GmbH.)

Breathing process involves inhalation and exhalation of different gases in animals. The gas exchange of the breathing process plays a critical role in maintaining the physiological functions of living organisms. Although artificial breathing materials exhibiting volume expansion and contraction upon alternate exposure to different gases have been well explored, those being able to realize the gas exchange remain elusive. Herein, we report breathing micelles (BM) capable of inhaling nitric oxide (NO) and exhaling carbon monoxide (CO), both of which are endogenous gaseous signaling molecules. We demonstrate that BM can simultaneously scavenge overproduced NO and attenuate proinflammatory cytokines in lipopolysaccharide (LPS)-challenged macrophage cells. In vivo studies revealed that BM outperformed conventional nonsteroidal anti-inflammatory drugs such as dexamethasone (Dexa) in treatment of rheumatoid arthritis (RA) in adjuvant-induced arthritis (AIA) rats, likely due to the combinatorial effect of NO depletion, CO-mediated deactivation of inducible NO synthase (iNOS) and activation of heme oxygenase-1 (HO-1). This work provides new insights into artificial BM for potential biomedical applications., (© 2020 Wiley-VCH GmbH.)

The emerging therapeutic potential of nitric oxide (NO) has spurred the rapid development of NO donors to maximize the therapeutic outcomes. Although polymeric NO donors have shown extended release times and optimized biodistributions, many of these macromolecular NO donors are non-degradable. Herein, we devise a macromolecular NO donor by integrating photoresponsive N,N'-dinitroso-p-phenylenediamine (DNP) derivatives into the middle block of an amphiphilic triblock copolymer and the photo-mediated NO release process transforms the DNP to quinondimine (QDI) moieties, enabling the degradation of the resulting polymers due to the spontaneous hydrolysis of QDI moieties. We demonstrated that the NO release process could be selectively activated under visible light irradiation both in vitro and in vivo. Moreover, the simultaneous release of NO and DOX could be achieved under visible light by taking advantage of the NO release-mediated micelle disassembly. This work provides new insights into the design of degradable macromolecular NO donors where the polymer breakdown could be actuated by triggered NO release.

The peroxynitrite anion (ONOO−) is closely associated with many diseases and the creation of ONOO− donors is an essential means of understanding its pathophysiological functions. However, it is challenging to develop ONOO− donors due to the difficulties in simultaneously producing highly reactive and short‐lived nitric oxide (NO) and superoxide anion (O2⋅−). Here, we report a novel strategy for constructing ONOO− donors by combining near‐infrared (NIR)‐mediated type I photosensitization and photoredox catalysis. The key design using a Nile blue analogue that can serve as both a type I photosensitizer and a metal‐free photocatalyst. Intriguingly, the formation of O2⋅− via type I photosensitization avoids oxygen interference and instead activates nitrobenzofurazan‐based NO donors via oxygen‐tolerant NIR photoredox catalysis. The simultaneous release of O2⋅− and NO leads to ONOO− release, showing both antibacterial and antibiofilm activities. [ABSTRACT FROM AUTHOR]

Photoredox catalysis has emerged as a robust tool for chemical synthesis. However, it remains challenging to implement photoredox catalysis under physiological conditions due to the complex microenvironment and the quenching of photocatalyst by biologically relevant molecules such as oxygen. Here, we report that UV‐absorbing N,N′‐dinitroso‐1,4‐phenylenediamine derivatives can be selectively activated by fac‐Ir(ppy)3 photocatalyst within micellar nanoparticles under visible light irradiation (e.g. 500 nm) through photoredox catalysis in aerated aqueous solutions to form quinonediimine (QDI) residues with concomitant release of NO. Notably, the formation of QDI derivatives can actively scavenge the reactive oxygen species generated by fac‐Ir(ppy)3, thus avoiding oxygen quenching of the photocatalyst. Further, we exemplify that the oxygen‐tolerant photoredox catalysis‐mediated NO release can not only kill planktonic bacteria in vitro but also efficiently treat MRSA infections in vivo. [ABSTRACT FROM AUTHOR]

Although nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) have been considered as notorious gas pollutants for decades, they are considered as endogenous gaseous signaling molecules (GSMs), which have been widely recognized for their important signaling functions and prominent medical applications in human physiology. To achieve local delivery of GSMs to optimize therapeutic efficacy and reduce systemic side effects, stimuli‐responsive nanocarriers have been successfully developed. Among them, ultrasound is considered as an attractive theranostic modality that can be used to track drug carriers, trigger drug release, and improve drug deposition, etc. In this minireview, recent achievements in designing ultrasound‐responsive nanocarriers for the controlled delivery of GSMs and their biomedical applications are summarized. This emerging research direction enables the controlled delivery of GSMs to deep tissues, and the combination of ultrasound imaging techniques offers many possibilities for the fabrication of new theranostic platforms. [ABSTRACT FROM AUTHOR]

The local delivery of gaseous signaling molecules (GSMs) has shown promising therapeutic potential. However, although GSMs have a subtle interplay in physiological and pathological conditions, the co‐delivery of different GSMs for therapeutic purposes remains unexplored. Herein, we covalently graft a nitric oxide (NO)‐releasing N‐nitrosamine moiety onto the carbon monoxide (CO)‐releasing 3‐hydroxyflavone (3‐HF) antenna, resulting in the first NO/CO‐releasing donor. Under visible light irradiation, photo‐mediated co‐release of NO and CO reveals a superior antimicrobial effect toward Gram‐positive bacteria with a combination index of 0.053. The synergy of NO and CO hyperpolarizes and permeabilizes bacterial membranes, which, however, shows negligible hemolysis and no evident toxicity toward normal mammalian cells. Moreover, the co‐release of NO and CO can efficiently treat MRSA infection in a murine skin wound model, showing a better therapeutic capacity than vancomycin. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) serves as a key regulator of many physiological processes and as a potent therapeutic agent. The local delivery of NO is important to achieve target therapeutic outcomes due to the toxicity of NO at high concentrations. Although light stimulus represents a non‐invasive tool with spatiotemporal precision to mediate NO release, many photoresponsive NO‐releasing molecules can only respond to ultraviolet (UV) or near‐UV visible light with low penetration and high phototoxicity. We report that coumarin‐based NO donors with maximal absorbances at 328 nm can be activated under (deep) red‐light (630 or 700 nm) irradiation in the presence of palladium(II) tetraphenyltetrabenzoporphyrin, enabling stoichiometric and self‐reporting NO release with a photolysis quantum yield of 8 % via photoredox catalysis. This NO‐releasing platform with ciprofloxacin loading can eradicate Pseudomonas aeruginosa biofilm in vitro and treat cutaneous abscesses in vivo. [ABSTRACT FROM AUTHOR]

Breathing process involves inhalation and exhalation of different gases in animals. The gas exchange of the breathing process plays a critical role in maintaining the physiological functions of living organisms. Although artificial breathing materials exhibiting volume expansion and contraction upon alternate exposure to different gases have been well explored, those being able to realize the gas exchange remain elusive. Herein, we report breathing micelles (BM) capable of inhaling nitric oxide (NO) and exhaling carbon monoxide (CO), both of which are endogenous gaseous signaling molecules. We demonstrate that BM can simultaneously scavenge overproduced NO and attenuate proinflammatory cytokines in lipopolysaccharide (LPS)‐challenged macrophage cells. In vivo studies revealed that BM outperformed conventional nonsteroidal anti‐inflammatory drugs such as dexamethasone (Dexa) in treatment of rheumatoid arthritis (RA) in adjuvant‐induced arthritis (AIA) rats, likely due to the combinatorial effect of NO depletion, CO‐mediated deactivation of inducible NO synthase (iNOS) and activation of heme oxygenase‐1 (HO‐1). This work provides new insights into artificial BM for potential biomedical applications. [ABSTRACT FROM AUTHOR]

Innentitelbild: Breathing Micelles for Combinatorial Treatment of Rheumatoid Arthritis (Angew. Keywords: anti-inflammatory; breathing micelles; carbon monoxide; nitric oxide; rheumatoid arthritis EN anti-inflammatory breathing micelles carbon monoxide nitric oxide rheumatoid arthritis 21974 21974 1 11/26/20 20201201 NES 201201 B Biomimetische "atmende" Mizellen b , die gleichzeitig Stickstoffoxid einatmen und Kohlenmonoxid ausatmen können, werden in der Zuschrift von T. You, J. Hu et al. auf S. 22048 vorgestellt. Anti-inflammatory, breathing micelles, carbon monoxide, nitric oxide, rheumatoid arthritis. [Extracted from the article]