| Bacterial and fungal infections are one of the severe challenges facing the world today.According to statistics,the number of deaths caused by pathogenic microorganisms such as bacteria,fungi,viruses and others have reached millions of people in the world,and showed an increasing trend year by year.Although traditional antibiotics have shown an excellent performance in inhibiting pathogenic microorganisms,which disrupt cell activity by affecting protein synthesis,genetic expression of DNA,and cell wall formation.They have limited ways to eradicate pathogens effectively and lack the selectivity,and it is easy to produce resistance to pathogens which greatly limit its antimicrobial efficiency.With the overuse of antibiotics,the problem of bacterial resistance has become more serious.The dosage of antibiotics has to be expanded in order to kill microorganisms effectively,which further exacerbates the severity of drug resistance problem.Antibiotic resistance will result in the death of patients and the heavy burden on medical system.The global economy will suffer huge losses,if the use of antibiotics is not strictly controlled or new antibacterial agents have not been developed.Nanomaterials have shown great potential in killing resistant bacterial as well as the application in drug delivery system due to the unique physical and chemical properties and structural advantages.It has found that the two-dimensional material has a large specific surface area,and the surface is easy to be functional modified.They shows great application value as a novel antimicrobial agent that is not easy to produce drug resistance.Mo S2 as a two-dimensional material,it is widely used in the biomedical field by virtue of good biocompatibility,high photothermal conversion efficiency and inherent mechanical properties.NO can participate in various physiological activities of human body as an endogenous gas signal molecule;furthermore,exogenous NO has confirmed that have excellent antimicrobial properties and no side effects.In order to achieve efficient loading and controlled release of NO,many carrier platforms have been constructed to maximize the performance of NO.Especially,the macromolecular NO release scaffold have been widely researched due to the higher payload and fixed-point release.Therefore,this paper conducts the following two parts based on the self-characteristic of Mo S2 and combined with the controlled release of NO:1.One-step synthesis of PEG-Mo S2 nanoflowers by hydrothermal method for killing P.aeruginosaP.aeruginosa is a pathogen that is very susceptible to infection by immunocompromised and critically ill patients in hospital,and the bacteremia caused by its infection has a higher mortality rate.As gram-negative bacteria,its outer membrane structure has low permeability of antibiotics,and quorum sensing can promote the formation of bacterial biofilms,which exacerbates the difficulty of post-infection treatment.In order to solve the above problems,Polyethylene glycol（PEG）modified molybdenum disulfide（Mo S2）nanoflowers were prepared by one-step hydrothermal synthesis method in this chapter.The morphology was characterized by TEM and confirmed the material is a nanoflower structure stacked by layers,and the successful preparation was further confirmed by elemental analysis using XPS.Antibacterial experiments in vitro and staining analysis showed that PEG-Mo S2had a concentration dependent bactericidal effect on P.aeruginosa,and effectively inhibit the formation of biofilm.The antibacterial mechanism was further analyzed,and the absorbance value of 260 nm was measured using an ultraviolet spectrophotometer to evaluate the integrity of the cell membrane,which confirmed that the material caused irreversible damage to bacterial cell membrane.SEM images intuitively verified the above results and indicated that the edge of the nanoflowers produced a sharp nano-knife effect,which directly interacted with bacterial and leading to mechanical death.ROS fluorescence analysis showed that the strong interaction between materials and bacteria caused high defect concentration and further resulted in the production of ROS,which enhanced the antibacterial activity.PEG-Mo S2 was proved to have good biocompatibility by cytotoxicity test,thus this nanoflower is expected to be a safe and efficient new antibacterial agent.2.Near-infrared light-induced NO release combined with low temperature photothermal effect of Mo S2 nanoflowers for synergistic antimicrobialS.aureus is a common symbiotic bacterial,the emergence of MRSA and VRSA due to antibiotics abuse in the past decades has further increased the risk of infection and the difficulty of treatment.Candida albicans is a ubiquitous pathogenic microorganism and a member of the symbiotic flora.Systemic infection by Candida albicans can lead to a high risk of death.In addition,more than a quarter of the world’s population suffered from fungal skin infections.To develop a new antimicrobial strategy for S.aureus and Candida albicans infections,on the basis of the first chapter,a hydrophobic small molecule NO donor BNN6 was introduced in this chapter.BNN6 was able to combined with PEG-Mo S2 through hydrophobic interaction force,and controlled release of NO was realized through near-infrared stimulation,thus effective antimicrobial activity was achieved by the coordination of NO and PTT.The successful preparation of BNN6 was confirmed by NMR.Nanoparticle size analyzer,UV-vis spectroscopy,and FITR spectrum were used to characterize the morphology,potential,particle size and chemical structure of PEG-Mo S2 before and after BNN6 loading,which verified the successful preparation of PEG-Mo S2-BNN6.The temperature of PEG-Mo S2-BNN6 rose rapidly after 808 nm laser irradiation with a power density of 1.5 W/cm2 for 10 min,and facilitated BNN6 decompose subsequently released plenty of NO.Moreover,NO release behavior also showed the controllability of the“switch”under intermittent NIR irradiation.In vitro antimicrobial experiments confirmed that the release of NO induced by NIR could effectively inhibit the growth of S.aureus and Candida albicans,and also confirmed the effective antimicrobial activity of PTT/NO.The possible mechanism could attribute to the increased permeability of microbial cell membrane after PTT treated,which improved the pass efficiency of NO through the cell membrane.NO entry into the cell and caused irreversible damage to microorganism,making the antimicrobial activity up to 99%.The cell viability staining analysis further indicated the integrity of cell membrane was changed after PEG-Mo S2-BNN6 and NIR treated,which was consistent with the results of antimicrobial experiments.SEM was used to observe the morphological change,and verified the antimicrobial mechanism derived from cell membrane damage and outflow of cell contents.Cytotoxicity test in vitro showed this system had good biocompatibility.This system effectively solved the key problems of low NO load,premature release and poor efficiency of monotherapy,and it expected to become a new antimicrobial agent to maximize the effectiveness of NO. |
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