Membrane‐Anchoring Photosensitizer with Aggregation‐Induced Emission Characteristics for Combating Multidrug‐Resistant Bacteria

Traditional photosensitizers (PSs) show reduced singlet oxygen (¹O₂) production and quenched fluorescence upon aggregation in aqueous media, which greatly affect their efficiency in photodynamic therapy (PDT). Meanwhile, non‐targeting PSs generally yield low efficiency in antibacterial performance due to their short lifetimes and small effective working radii. Herein, a water‐dispersible membrane anchor (TBD‐anchor) PS with aggregation‐induced emission is designed and synthesized to generate ¹O₂ on the bacterial membrane. TBD‐anchor showed efficient antibacterial performance towards both Gram‐negative (Escherichia coli) and Gram‐positive bacteria (Staphylococcus aureus). Over 99.8 % killing efficiency was obtained for methicillin‐resistant S. aureus (MRSA) when they were exposed to 0.8 μm of TBD‐anchor at a low white light dose (25 mW cm^?2) for 10 minutes. TBD‐anchor thus shows great promise as an effective antimicrobial agent to combat the menace of multidrug‐resistant bacteria.     

A Cross‐linked Conjugated Polymer Photosensitizer Enables Efficient Sunlight‐Induced Photooxidation

Photooxidation under sunlight has potential in organic synthesis, bacterial killing, and organic waste treatment. Photosensitizers (PSs) can play an important role in this process. High ¹O₂ generation efficiency and excellent photostability under sunlight, as well as easy recyclability are ideal properties for PSs, but are not easy to achieve simultaneously. Herein, a pure organic porous conjugated polymer PS, CPTF, shows great photostability, large specific surface area, and high ¹O₂ generation efficiency under sunlight for photooxidation. For the oxidation of aromatic aldehyde to aromatic acid, the PS catalyst shows excellent recyclability, and enables solvent‐free reactions in high yields both under direct sunlight and simulated AM 1.5G irradiation. In addition, the successful application of CPTF as an antibacterial agent and organic waste decomposition under simulated AM 1.5G irradiation indicates the potential of CPTF in sunlight‐induced waste water treatment.     

Novel 3‐Hydroxy‐2‐naphthoic hydrazone and Ni(II), Co(II) and Cu(II) Complexes: Synthesis,Spectroscopic Characterization,Antimicrobial, DNA Cleavage and Computational Studies

A novel hydrazone ligand derived from condensation reaction of 3‐hydroxy‐2‐naphthoic hydrazide with dehydroacetic acid, and its Ni(II), Cu(II) and Co(II) complexes were synthesized, characterized by spectroscopic, elemental analyses, magnetic susceptibility and conductivity methods, and screened for antimicrobial, DNA binding and cleavage properties. Spectroscopic analysis and elemental analyses indicated the formula, [MLCl₂], for the complexes; square planar geometry for the nickel, and tetrahedral geometry for copper and cobalt complexes. The non‐electrolytic natures of the complexes in Dimethyl Sulphoxide (DMSO) were confirmed by their molar conductance values in the range of 6.11–14.01 Ω^?1cm²mol^?1. The copper complex had the best antibacterial activity against Staphylococcus aureus (ATCC 29213). DNA cleavage activities of the compounds, evaluated on pBR322 DNA, by agarose gel electrophoresis, in the presence and absence of oxidant (H₂O₂) and free radical scavenger (DMSO), indicated no activity for the ligand, and moderate activity for the complexes, with the copper complex cleaving pBR322 DNA more efficiently in the presence of H₂O₂. When the complexes were evaluated for antibacterial and A‐DNA activity using Molecular docking technique, the copper complex was found to be most effective against Gram‐positive (S. aureus) bacteria. [CuLCl₂] showed good hydrogen bonding interaction with the major‐groove (C₂^.G₁₃ base pair) of A‐DNA. Density functional theory (DFT) calculations of the structural and electronic properties of the complexes revealed that [CuLCl₂] had a smaller HOMO‐LUMO gap, suggesting a higher tendency to donate electrons to electron‐accepting species of biological targets.     

A Targeting Singlet Oxygen Battery for Multidrug-Resistant Bacterial Deep-Tissue Infections

Traditional photodynamic therapy (PDT) is dependent on externally applied light and oxygen, and the depth of penetration of these factors can be insufficient for the treatment of deep infections. The short half-life and short diffusion distance of reactive oxygen species (ROS) also limit the antibacterial efficiency of PDT. Herein, we designed a targeting singlet oxygen delivery system, CARG-Py, for irradiation-free and oxygen-free PDT. This system was converted to the “singlet oxygen battery” CARG-¹O₂ and released singlet oxygen without external irradiation or oxygen. CARG-¹O₂ is composed of pyridones coupled to a targeting peptide that improves the utilization of singlet oxygen in deep multidrug-resistant bacterial infections. CARG-¹O₂ was shown to damage DNA, protein, and membranes by increasing the level of reactive oxygen inside bacteria; the attacking of multiple biomolecular sites caused the death of methicillin-resistant Staphylococcus aureus (MRSA). An in vivo study in a MRSA-infected mouse model of pneumonia demonstrated the potential of CARG-¹O₂ for the efficient treatment of deep infections. This work provides a new strategy to improve traditional PDT for irradiation- and oxygen-free treatment of deep infections while improving convenience of PDT.     

Methylene Blue/Carbon Dots Composite with Photothermal and Photodynamic Properties: Synthesis,Characterization, and Antibacterial Application

Photodynamic therapy and photothermal therapy provide new ways to combat antibiotic resistance. In this research, methylene blue (MB) as an effective photosensitizer was conjugated with carbon quantum dots (CQDs), the composite product not only possessed good antibacterial properties against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) due to excellent singlet oxygen (¹O₂) production rate and light heat transfer performance, but also showed good biocompatibility. Combined with 808 nm and 660 nm laser irradiation, the minimum bactericidal concentration of CQDs-MB towards S. aureus and E. coli was 5 μm . Therefore, this study provides a potential candidate material based on CQDs for clinical applications.     

Diketopyrrolopyrrole Derivatives as Photosensitizing Agents against Staphylococcus aureus

Diketopyrrolopyrrole (DPP) derivatives containing sulfonamide ( Sulfonamide-DPP ), pyridyl ( Dipyridyl-DPP ) and N-methylpyridyl ( MePyridyl-DPP ) substituents were assessed as antibacterial photosensitizers. Non-charged DPPs showed an intense absorption band centered at about 480 nm and green fluorescence emission (Φ_F ~ 0.7) in acetonitrile. The absorption of MePyridyl-DPP was bathochromically shifted at 510 nm, with decreased fluorescence emission. Sulfonamide-DPP and Dipyridyl-DPP photosensitized the formation of O₂(¹Δ_g) (Φ_Δ ~ 0.15–0.17), while the production induced by MePyridyl-DPP was at least 10 times lower. Furthermore, these DPPs produced a photoreduction of NBT similar to that of the control. Photodynamic inactivation induced by DPPs was first investigated at the single-bacterium level of Staphylococcus aureus attached to a surface. After 30 min irradiation, MePyridyl-DPP produced a complete eradication of the bacteria. In bacterial cell suspensions, dicationic DPP induced more than 7 log₁₀ decrease in S. aureus cell survival after 30 min irradiation. Potentiation with iodide anions allowed a complete elimination of bacteria after 15 min therapy. This compound was also effective to eliminate S. aureus cells on biofilms. The results show that MePyridyl-DPP bearing two positive groups provides an amphiphilic character to the structure that improves the interaction with the cell envelop. This effect enhances the photocytotoxic activity of MePyridyl-DPP against bacteria.     

Structural Element of Vitamin U-Mimicking Antibacterial Polypeptide with Ultrahigh Selectivity for Effectively Treating MRSA Infections

Antimicrobial peptides (AMPs) exhibit mighty antibacterial properties without inducing drug resistance. Achieving much higher selectivity of AMPs towards bacteria and normal cells has always been a continuous goal to be pursued. Herein, a series of sulfonium-based polypeptides with different degrees of branching and polymerization were synthesized by mimicking the structure of vitamin U. The polypeptide, G₂-PM-1^H+, shows both potent antibacterial activity and the highest selectivity index of 16000 among the reported AMPs or peptoids (e.g., the known index of 9600 for recorded peptoid in “Angew. Chem. Int. Ed., 2020, 59, 6412.”), which can be attributed to the high positive charge density of sulfonium and the regulation of hydrophobic chains in the structure. The antibacterial mechanisms of G₂-PM-1^H+ are primarily ascribed to the interaction with the membrane, production of reactive oxygen species (ROS), and disfunction of ribosomes. Meanwhile, altering the degree of alkylation leads to selective antibacteria against either gram-positive or gram-negative bacteria in a mixed-bacteria model. Additionally, both in vitro and in vivo experiments demonstrated that G₂-PM-1^H+ exhibited superior efficacy against methicillin-resistant Staphylococcus aureus (MRSA) compared to vancomycin. Together, these results show that G₂-PM-1^H+ possesses high biocompatibility and is a potential pharmaceutical candidate in combating bacteria significantly threatening human health.     

Spectral characterization and antibacterial effect of 2-methyl-6-(5-H-Me-Cl-NO <Subscript>2</Subscript>-1<Emphasis Type="Italic">H</Emphasis>-benzimidazol-2-yl)-phenols and some transition metal complexes

2-Methyl-6-(5-H-methyl-chloro-nitro-1H-benzimidazol-2-yl)-phenols( HL _x :x= 1-4)ligands and HL₁ complexes with Fe(NO₃)₃, Cu(NO₃)₂, AgNO₃, Zn(NO₃)₂ have been synthesized and characterized. The structures of the compounds were confirmed on the basis of elemental analysis, molar conductivity, magnetic moment, FT-IR, ¹H-and ¹³C-NMR. Antibacterial activity of the free ligands, their hydrochloride salts and the complexes were evaluated using the disk diffusion method in dimethyl sulfoxide as well as the minimum inhibitory concentration dilution method, against nine bacteria. While HL₁ ligand has not any activity, it’s Ag(I) complex show antibacterial effect toward almost to all the bacteria. Zn(II) complex has antibacterial effect on especially K. pneumoniae, S. epidermidis and S. aureus bacteria.     

Time-Dependent Photodynamic Therapy for Multiple Targets: A Highly Efficient AIE-Active Photosensitizer for Selective Bacterial Elimination and Cancer Cell Ablation

Pathogen infections and cancer are two major human health problems. Herein, we report the synthesis of an organic salt photosensitizer (PS), called 4TPA-BQ, by a one-step reaction. 4TPA-BQ presents aggregation-induced emission features. Owing to the aggregation-induced reactive oxygen species generated and a sufficiently small ΔE_ST, 4TPA-BQ shows a satisfactorily high ¹O₂ generation efficiency of 97.8 %. In vitro and in vivo experiments confirmed that 4TPA-BQ exhibited potent photodynamic antibacterial performance against ampicillin-resistant Escherichia coli with good biocompatibility in a short time (15 minutes). When the incubation duration persisted long enough (12 hours), cancer cells were ablated efficiently, leaving normal cells essentially unaffected. This is the first reported time-dependent fluorescence-guided photodynamic therapy in one individual PS, which achieves ordered and multiple targeting simply by varying the external conditions. 4TPA-BQ reveals new design principles for the implementation of efficient PSs in clinical applications.     

Peroxidase-Mimetic Copper-Doped Carbon-Dots for Oxidative Stress-Mediated Broad-Spectrum and Efficient Antibacterial Activity

Carbon dots (CDs) have recently emerged as antibacterial agents and have attracted considerable attention owing to their fascinating merits of small size, facile fabrication, and surface functionalization. Most of them are involved in external light activation or hybridization with other functional nanomaterials. Herein, we present peroxidase-like Cu-doped CDs (Cu-CDs) for in vitro antibacterial applications. The unique peroxidase-mimicking property of the Cu-CDs was demonstrated by tetramethylbenzidine chromogenic assay, electron paramagnetic resonance spectra, and hydroxy radical probe. Escherichia coli and Staphylococcus aureus were chosen as representative gram-negative/positive models against which Cu-CDs exhibited superior antimicrobial activity even at a dosage down to 5 μg/mL. A possible mechanism of action was that the Cu-CDs triggered a catalytic redox reaction of endogenous H₂O₂ and glutathione depletion in the bacteria cells, with subsequent oxidative stress and membrane disruption. This work provides a new strategy for the design of microenvironment-responsive antimicrobial nano-agents.     

Antioxidant,antimicrobial, and tyrosinase inhibition activities of acetone extract of <Emphasis Type="Italic">Ascophyllum nodosum</Emphasis>

The search for new antioxidants of natural origin derived from plants and seaweeds is still very important at present. In our study, the acetone extract of A. nodosum was investigated for its potential use as a natural antioxidant, natural feed additive with antibacterial activity and as a tyrosinase inhibitor. This study could be useful in the context of improved utilization of the A. nodosum extract in the food and cosmetics industry, being not only economically advantageous but also environmentally friendly. Extracts showed antioxidant activity with application of different methodologies: 1,1-diphenyl-2-picrilhydracil DPPH· radicals scavenging (39 %, 4 mg of freeze-dried sample), β-carotene-linoleic acid antioxidant assay (11 %, 4 mg of freeze-dried sample), O₂· radicals scavenging activity (IC₅₀ 0.43 mg mL⁻¹), OH· radicals scavenging activity (IC₅₀ 1.55 mg mL⁻¹), and iron chelation ability (IC₅₀ 0.56 mg mL⁻¹). The extract showed considerable antibacterial activity being more effective against gram-positive bacteria (Micrococcus luteus, Staphylococcus aureus) than against gram-negative bacteria (Escherichia coli, Enterococcus aerogenes). Results of tyrosinase assay for the acetone extract of Ascophyllum nodosum presented 65.6 % inhibition of tyrosinase activity at the IC₅₀ value of 0.1 mg mL⁻¹. The outcomes of our study support potential utilization of this brown seaweed as a source of natural antioxidants. Antioxidant activity of the studied seaweed can be apparently explained by the free radicals scavenging activity, particularly related to the mechanisms of O₂⁻· radicals scavenging activity, OH· radicals inactivation, and iron chelation ability.     

Preparation,Antibacterial Activity,and Catalytic Application of Magnetic Graphene Oxide-Fucoidan in the Synthesis of 1,4-Dihydropyridines and Polyhydroquinolines

Polymer-coated magnetic nanoparticles are emerging as a useful tool for a variety of applications, including catalysis. In the present study, fucoidan-coated magnetic graphene oxide was synthesized using a natural sulfated polysaccharide. The prepared BaFe₁₂O₁₉@GO@Fu (Fu=fucoidan, GO=graphene oxide) was characterized using Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) analysis, vibrating sample magnetometry (VSM), thermogravimetric analysis (TGA), Raman spectroscopy, and X-ray diffraction (XRD). The catalytic proficiency of BaFe₁₂O₁₉@GO@Fu was investigated in the synthesis of 1,4-dihydropyridine and polyhydroquinoline derivatives. Excellent turnover numbers (TON) and turnover frequencies (TOF) (6330 and 25320 h⁻¹) testify to the high efficiency of the catalyst. Moreover, the antimicrobial activity of BaFe₁₂O₁₉@GO@Fu was evaluated against Escherichia coli (E. coli), and Staphylococcus aureus (S. aureus) through the Agar well diffusion method, indicating that BaFe₁₂O₁₉@GO@Fu has antibacterial activity against S. aureus.     

Antibacterial ultrafiltration membrane with silver nanoparticle impregnation by interfacial polymerization for ballast water

Interfacial polymerization technology was employed to immobilize silver (Ag) nanoparticles on the surface of commercial polyethersulfone (PES) membrane to develop antibacterial and antifouling ultrafiltration membrane. Ag nanoparticles were prepared from the reduction of silver nitrate (AgNO₃) by sodium borohydride in the presence of polyethyleneimine (PEI) as the stabilizer. The encapsulated Ag nanoparticles in the PEI solution were embedded into the PEI membrane when trimesoyl chloride solution was used to crosslink the PEI solution with the PES membrane, forming Ag-polyamide (PA) networks through the interfacial polymerization reaction. Experimental results showed that the membrane prepared with 50 mmol/L of AgNO₃ and 20 mmol/L of PEI had the optimized antibacterial effect against Escherichia coli. Bacterial concentration and species were also investigated. Exiguobacterium aestuarii and Staphylococcus aureus which are gram-positive bacteria, needed significantly more time for the Ag-PA/PES membrane to kill the bacteria completely when compared to E.coli and Vibrio coralliilyticus which are gram-negative bacteria. This study showed that Ag nanoparticles impregnated in membrane surfaces were 100% effective in killing various types of marine bacteria and bacteria in the seawater collected off Sentosa Island in Singapore. These membranes exhibit excellent antibacterial and antifouling properties which can be used to kill bacteria in ballast water and seawater.     

A novel Ag/Ag3PO4-IRMOF-1 nanocomposite for antibacterial application in the dark and under visible light irradiation

MOF-5 that sometimes called IRMOF-1 has been intensively studied in recent years to develop efficient photocatalyst to degrade refractory organics and inactivate bacteria for wastewater treatment. In the present work, Ag/Ag₃PO₄ nanoparticles incorporated in IRMOF-1 was successfully prepared via hydrothermal approach. The antibacterial activity of synthesized materials (IRMOF-1, Ag/Ag₃PO₄ nanoparticles and Ag/Ag₃PO₄-IRMOF-1 nanocomposite was compared against two types of bacteria (Escherichia coli (E. coil) as Gram negative and Staphylococcus aureus (S. aureus) as Gram-positive bacteria). The deactivation of the bacteria by the prepared material was measured in the dark and under visible light irradiation. The antibacterial activity of synthesized samples was investigated by determining the minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), growth inhibition assay and inhibition zone. The Ag/Ag₃PO₄-IRMOF-1 nanocomposite exhibited stronger antibacterial activities than the Ag/Ag₃PO₄ nanoparticles and IRMOF-1 at all tested bacteria types. Based on inhibition zone, without any light irradiation, Ag/Ag₃PO₄-IRMOF-1 nanocomposite showed activity toward E. coil, but in presence of light nanocomposite depicted activity toward S. aureus. The results demonstrated that antibacterial activity of all synthesized samples in the dark and light against S. aureus bacteria was more than E. coil bacteria. The antibacterial activity mechanism was due to sustained-release of silver ions in the dark and reactive oxygen species (ROS) under visible light. The bioactivity of IRMOF-1 was related to the degradation of the its structure and the release of Zn²⁺ ions into the culture medium that bind to the cell wall and deactivation bacteria.     

In Vitro Photodynamic Inactivation Effects of Ru(II) Complexes on Clinical Methicillin‐resistant Staphylococcus aureus Planktonic and Biofilm Cultures

Photosensitizers (PSs) combined with light are able to generate antimicrobial effects. Ru(II) complexes have been recognized as a novel class of PSs. In this study, we investigated the effectiveness of photodynamic inactivation (PDI) mediated by three Ru(II) polypyridine complexes, 1–3, against four isolates of clinical methicillin‐resistant Staphylococcus aureus (MRSA‐1, MRSA‐2, MRSA‐3 and MRSA‐4). In PDI of a planktonic culture of MRSA‐1, compound 3 showed the highest efficacy, likely owing to its advantageous light absorption, ¹O₂ quantum yield and bacterial cellular binding. The PDI efficacy of 3 was further evaluated against all other strains and MRSA‐1 biofilms. At appropriate PS concentrations, viability reduction of 100% or 96.83% was observed in planktonic or biofilm forms of MRSA, respectively. The mechanisms of action were investigated using negative staining transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). It was demonstrated that PDI of planktonic bacteria was achieved primarily through damage to the cell envelope. Biofilms were eliminated through both the destruction of their structure and inactivation of the individual bacterial cells. In conclusion, Ru(II) complexes, especially 3, are potential candidates for the effective photodynamic control of MRSA infections.     

Encapsulation of Pd(II) by N4 and N2O2 macrocyclic ligands: their use in catalysis and biology

New macrocyclic Schiff base Pd(II) compounds were synthesized by treating N₄ and N₂O₂ macrocycles with palladium chloride in a 1 : 1 ratio. The resulting macrocyclic compounds were characterized by elemental, IR, ¹H-NMR, ¹³C-NMR, mass, molar conductance, magnetic susceptibility, electronic spectra, and thermal analysis. These compounds were used as catalysts in the development of an efficient catalytic method for reduction of organic substrates having nitro, olefinic, acetylenic, and aldehyde groups under mild reaction conditions. The biological activities of all the macrocycles and macrocyclic Pd(II) compounds have been tested against gram positive (Bacillus subtilis and Staphylococcus aureus) and gram negative (Escherichia coli and Klebsiella pneumonia) bacteria and found to be more active than commercially available antibacterial drugs like Streptomycin and Ampicillin.     

Time‐Dependent Photodynamic Therapy for Multiple Targets: A Highly Efficient AIE‐Active Photosensitizer for Selective Bacterial Elimination and Cancer Cell Ablation

Pathogen infections and cancer are two major human health problems. Herein, we report the synthesis of an organic salt photosensitizer (PS), called 4TPA‐BQ, by a one‐step reaction. 4TPA‐BQ presents aggregation‐induced emission features. Owing to the aggregation‐induced reactive oxygen species generated and a sufficiently small ΔE_ST, 4TPA‐BQ shows a satisfactorily high ¹O₂ generation efficiency of 97.8 %. In vitro and in vivo experiments confirmed that 4TPA‐BQ exhibited potent photodynamic antibacterial performance against ampicillin‐resistant Escherichia coli with good biocompatibility in a short time (15 minutes). When the incubation duration persisted long enough (12 hours), cancer cells were ablated efficiently, leaving normal cells essentially unaffected. This is the first reported time‐dependent fluorescence‐guided photodynamic therapy in one individual PS, which achieves ordered and multiple targeting simply by varying the external conditions. 4TPA‐BQ reveals new design principles for the implementation of efficient PSs in clinical applications.     

Preparation and Spectral and Biological Investigation of vic-Dioxime Ligands Containing Piperazine Moiety and Their Mononuclear Transition-Metal Complexes

Two vic-dioxime ligands, N-(4-benzylpiperazine-1-yl) p-tolylglyoxime (L¹H₂) and N,N′-bis(4-benzylpiperazine-1-yl) glyoxime (L²H₂), containing piperazine moieties were synthesized, and their Ni(II), Cu(II), Co(II) and Zn(II) complexes were obtained. The ligands were characterized by elemental analysis, Fourier transform–infrared (FT-IR), ultraviolet–visible NMR (¹H, ¹³C, and heteronuclear multiple-bond correlation), and electrospray ionization (ESI) mass spectrometry. The isolated complexes were characterized by a combination of elemental analysis, IR, UV-vis, and ESI mass spectrometry and in the case of Ni(II) and Zn(II) complexes by ¹H and ¹³C NMR spectroscopy. The electrochemical behaviors of the ligands and their complexes were studied by cyclic voltammetry (CV) in dimethylsulfoxide solution containing tetrabutylammoniumtetrafluoroborate (TBATFB). The antibacterial activity was also studied against S. aureus ATCC 25923, S. aureus ATCC 29213, S. mutans RSHM 676, E. faecalis ATCC 29212, E. coli ATCC 25922, and P. aeruginosa ATCC 27853. The antimicrobial test results indicated that all the compounds have good antibacterial activity against P. auriginosa ATCC 27853 bacteria and were as effective as ampicilin.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resources: Full experimental and spectral details.]     

Design,synthesis and biological evaluation of novel N1,N8-bis(((4-((5-aryl-1,3,4-oxadiazol-2-yl)methoxy)phenyl)amino)oxy)-1-naphthamide derivatives

A new series of 1,8-bis(4-((5-phenyl-1,3,4-oxadiazol-2-yl) methoxy)-substituted aryl) naphthalene-1,8-dicarboxamide derivatives (6a–j) were synthesized in the presence of POCl₃ and obtained good yields. All the synthesized novel compounds were characterized by IR, ¹H NMR, ¹³C NMR, HRMS spectroscopic data and elemental analysis. All the synthesized compounds evaluated for their antibacterial and antifungal activities. The antibacterial activity screened against Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli and used standard reference drug ciprofloxacin. The antifungal activity screened against two pathogenic fungal strains Aspergillus niger and Candida albicans used a reference standard drug Voriconazole. All these compounds (6a–j) demonstrate good antibacterial and antifungal activity. Among them, compounds 6h and 6c show highest antibacterial and antifungal activity.     

In Situ Sprayed Difunctional Gel Avoiding Microenvironments Limitations to Treat Pressure Ulcers

How to avoid the microenvironment limitations in the therapeutic process of pressure ulcers is still challenging. The development of a functional gel can kill bacteria and scavenge reactive oxygen species (ROS), which is urgently required in the therapeutic process of pressure ulcers. Herein, an in situ sprayed gel is developed with silver nanoparticles (AgNPs) and polydopamine (PDA) NPs (APG) to obviate microenvironment restrictions in treating pressure ulcers. The gel is constructed by spraying sodium alginate solution and CaCl₂ solution. AgNPs serve as an antibacterial agent in the formed gel, which can effectively cause bacterial inactivation and show more than 5 log (>99.999%) bacterial killing efficiency against methicillin-resistant S. aureus (MRSA), Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli) in vitro. Meanwhile, PDA NPs serve as the antioxidative agent in the formed gel, which can facilitate the elimination of ROS to address the high ROS problem in wound microenvironment. Based on these features, it is demonstrated through cell and animal experiments that the AgNPs and PDA NPs incorporated gel can realize the effective treatment of MRSA-infected and hydrogen peroxide (H₂O₂)-sensitized pressure ulcers. It is believed that the designed system by a simple spray-coating approach can provide a new therapeutic strategy in biomedical areas.