Preparation Of Novel Antibacterial Nanocomposites And Their Application In The Treatment Of Bacterial Infections

With the increasingly serious threat of bacterial infections,especially for antibiotic-resistant bacterial infections,the development of highly effective treatment modalities to inhibit drug-resistant(DR)bacterial infections is of great urgency.Nanomaterials with unique antibacterial mechanism show great potential for fighting DR bacterial infections.Although silver nanoparticles(Ag NPs)with broad-spectrum antimicrobial properties have been intensively applied as antibacterial agent,instability of silver nanoparticles results in an unsatisfactory therapeutic efficacy toward DR bacterial infections.Therefore,it is of great significance to design the traditional silver nanoparticles to improve its stability and antibacterial ability.Based on the advantages of good dispersion,high biocompatibility and simple preparation of graphene quantum dots(GQDs),we constract GQDs@Ag nanocomposites with improved dispersion and antibacterial ability and study its antibacterial application.Meanwhile,based on the advantages of good biocompatibility and high photothermal ability of Prussian blue(PB),we constract synergistically multifunctional nanosystem of PB@PDA@Ag which combines photothermal therapy and silver nanoparticles and study its antibacterial application.The main contents of this research are as follow:1.Preparation and application of GQDs@Ag nanocomposites.Firstly,we prepared GQDs by a green and simple hydrothermal method with the natural polymer starch as a precursor for uniformly decorating Ag NPs to form GQDs@Ag.GQDs@Ag was characterized by transmission electron microscopy,Zeta particle size,X-ray diffraction,X-ray photoelectron spectroscopy,ultraviolet-visible spectrophotometer,and Fourier infrared spectroscopy.In vitro antibacterial ability of GQDs@Ag toward E.coli,S.aureus and MRSA was evaluated by agar diffusion test,turbidity method,optical density method,fluorescent staining method,scanning electron microscope,ATP assay and protein leakage assay.We established a Balb/c mice MRSA-infected wound model to evaluate in vivo antibacterial ability and safety of GQDs@Ag.In vivo wound healing effect and antibacterial ability of GQDs@Ag were evaluated by monitoring wound closure and inflammatory response.In vivo biosafety of GQDs@Ag was evaluated by blood biochemical analysis and histopathological alanalysis.The above results show that we have successfully prepared GQDs@Ag with improved stability and antibacterial ability.GQDs@Ag can kill DR bacteria by destroying the bacterial membrane,inducing reactive oxygen species,declining level of ATP,and causing protein leakage.Moreover,GQDs@Ag can more effectively promote wound healing with negligible toxicity for mice.2.Preparation and application of PB@PDA@Ag nanocomposites.Firstly,PB was prepared by hydrothermal method,and further modified with polydopamine and in-situ growth of Ag NPs to prepare PB@PDA@Ag nanocomposites.PB@PDA@Ag was characterized by the methods in paragraph 1.Photothermal effect of PB@PDA@Ag was evaluated by NIR laser.In vitro antibacterial ability of PB@PDA@Ag combined with NIR light toward E.coli,S.aureus,Amp~r E.coli and MRSA was evaluated by plate method as well as the methods in paragraph 1.We established Balb/c and MKR mice MRSA-infected wound model to evaluate in vivo antibacterial ability and safety of PB@PDA@Ag combined with NIR light.In vivo wound healing effect and antibacterial ability of combinational strategy were evaluated by monitoring wound closure,inflammatory response,bacterial CFU and VEGF expression level.In vivo biosafety of PB@PDA@Ag was evaluated by blood biochemical analysis and histopathological alanalysis.The above results show that we have successfully prepared PB@PDA@Ag with photothermal effect.Compared with single-mode strategy of PB@PDA@Ag or photothermal therapy,combinational strategy shows higher antibacterial ability.Combinational strategy can kill DR bacteria by destroying the bacterial membrane,inducing reactive oxygen species,declining level of ATP,and causing protein leakage.Moreover,combinational strategy can more effectively promote the healing of chronic wounds by removing bacteria of wound tissues,inducing the expression of VEGF and mitigating inflammatory response with negligible toxicity for mice.In summary,we successfully prepared GQDs@Ag nanocomposites and photothermal PB@PDA@Ag nanocomposites with high anti-DR bacteria and promoting wound healing ability.This study provides a promising candidate for the clinical treatment of DR bacterial infections.