Responsive Selenium Nanosystem And Ruthenium Cascade Antibacterial Nanosystem For The Treatment Of Bacterial Infections

Although antibiotics have achieved great success in the treatment of infectious diseases,bacterial infections are still a worldwide public health issue today.Because the mechanisms by which bacteria destroy the host's immune system are complex and they can prevent antibiotics from reaching the infection site,the eradication of certain diseases?such as pneumonia,tuberculosis,sepsis,etc.?faces great challenges.The current clinical treatment process lacks effective antibacterial drugs,and some powerful antibiotics can cause serious side effects.Therefore,they are only administered when the patient is severely infected.In addition,the emergence of highly infectious and highly lethal DR strains puts patients at risk of death.In the past few decades,nanosystems have shown many advantages in related research,such as good solubility,prolonged circulation time,the efficacy of slow-release,controlled-release,and combination therapy.Many nanodrugs have been approved for clinical treatment of various infectious diseases,and some nano antibacterials have also entered various stages of clinical trials.Therefore,it is of far-reaching application prospects to use nanomaterials either as effective antibacterial agents or as a delivery platform to build nanoantibacterial systems to replace antibiotics.According to the above research background,two different types of nanosystems against bacterial infections were designed and prepared in this paper,bacterial-responsive selenium bionic nanosystem and ruthenium-based cascade hybrid nanosystem,and their ability to monitor and treat bacterial infections in real time and to promote wound healing of bacterial infections in vivo were studied,repectively.This paper consists of three chapters:Chapter 1:Introduction,starting from the main structure of bacteria and the mechanism of drug resistance,we introduce the problem of bacterial infection which is currently urgently needed to be solved.Then introduced the different antibacterial mechanisms of nanomaterials according to the structure and characteristics of bacteria,and the classification of common nanomaterials.The research progress of nanomaterials as active therapeutic agents and responsive therapeutic systems was also mainly introduced.Finally,the research progress,deficiencies and research prospects of nanosystem in the field of combating bacterial infections are described.In chapter 2,A biomimetic multifunctional antibacterial nanosystem?Ru-Se@G NPs-RBCM?was designed and synthesized.The red blood cell membrane?RBCM?exerted its bionic properties,and gave the nano-immune escape ability.After reaching the MRSA infection micro-environment,the bacterial exotoxin was removed,and then the nano-core?Ru-Se@G NPs?that can be specifically degraded by metal matrix proteases was exposed.Then in response to the highly expressed gelatinase,the ruthenium complex functionalized selenium NPs?Ru-Se NPs?was released,ultimately achieving synergistic antibacterial and real-time in vivo imaging.In vitro experiments showed that the Ru-Se@G NPs-RBCM nano system can escape the phagocytosis of macrophages,effectively reduce the toxin hemolytic activity of MRSA secretion,respond to enzymes and bacteria,and specifically release Ru-Se NPs,achieving a highly effective synergistic bactericidal effect.The mice model also showed that,it could monitor the progress of infection treatment,and effectively promote wound healing of MRSA infection as well.In chapter 3,A hybrid antibacterial system?Ru NFs/GOx?based on ruthenium nanoframe?Ru NFs?was constructed as a cascade reagent with good biocompatibility and self-activating effect,and the outer layer was further modified with hyaluronic acid?HA?,which was used to achieve the bacterial infection micro-environment responsive treatment in vivo.Natural glucose oxidase?GOx?was loaded in Ru NFs by physical adsorption.When excessive hyaluronidase?HAase?secreted by bacteria in mouse wounds degrades the outer layer of HA,Gox,as a start enzyme,continuously convert non-toxic glucose into gluconic acid and H₂O₂,which could reduce toxic side effects.At the same time,the gluconic acid produced could change the p H value to 3?4,and then activate the peroxidase-like activity of Ru NFs.Subsequently,the accumulated H₂O₂will be converted into the hydroxyl radical?·OH?with stronger antibacterial performance,and eventually induce the bacterial death in synergy.In vivo studies showed that the prepared hybrid nanosystem exerted the advantages of promoting infection wound healing and high biological safety.