| The treatment of bacterial infections is one of the most challenging tasks in the biomedical field. Antibiotics have been developed for more than 70 years, and are considered to be the most effective drugs for the treatment of bacterial infections. However, due to the misuse of antibiotics, multi-drug resistant super bacteria appear at an unprecedented rate in the world, and threaten public health. Including Gram-positive vancomycin resistant(VRE), resistant to Staphylococcus aureus(MRSA) and Gram-negative multi-drug resistant(MDR) Klebsiella pneumoniae, Acinetobacter, Pseudomonas aeruginosa, and Enterobacter, referred to as "ESKAPE".The emergence of these problems prompted chemists to continue to seek new strategies, and one of the most promising is the Nano-drugs. Compared with traditional molecular medicine, the advantages of Nano-drug: Nano-drugs have a small size effect of Nano-particles, easy to enter the cell; Nano-drugs with large surface area, functional groups or active centers can be used to link to or carrier; Excellent performance of Nano-drugs, easy to facilitate biodegradation or absorption; Due to their porous, hollow, multi-layer and other structural properties of nanoparticles, can be used to drug delivery et al.Based on the previous work, two different types of nanoparticles, w multifunctional selenium nanoparticle and ruthenium nanoparticle, which have the function of target to the bacteria surface, were designed and synthesized. The ability of these nanoparticles against MDR bacteria was studied systematically, aimed to seek the potential of Nano-drugs which can against MDR bacteria.The full paper is divided into three chapters:In chapter 1, we first describe the mechanism of MDR bacteria and the approaches to overcome MDR, and then focus on the present research methods and progress development of nanoparticles in overcoming MDR bacteria, Finally, we point out the challenges, difficulties and future prospects of the current treatment of MDR bacteria and give the purpose and significance of this thesis.In chapter 2, selenium nanoparticles(Qu-Ach@SeNPs) modified with quercetin and acetylcholine chloride were synthesized and characterized. Quercetin has been reported to exhibit a wide range of biological activities related to their antibacterial activity and acetylcholine as a targeting compound, which can combine with the receptor on the bacterial cell. The study demonstrated Qu-Ach@SeNPs exhibited a synergistically enhanced antibacterial performance against the multidrug-resistant superbugs. Qu-Ach@SeNPs attached to the bacterial cell wall, and reactive oxygen species produce, causing irreversible damage to the membrane, and killed them. Such as, methicillin-resistant Staphylococcus aureus(MRSA).In chapter 3, ruthenium nanoparticles(Ach@Ru NPs) modified by acetylcholine which have the function of target to the bacteria surface, were synthesized and characterized. We investigated the effect of Ach@RuNPs on bacterial photodynamic therapy(PTT) and photodynamic therapy(PDT). The results show that Ach@RuNPs has good photodynamic therapy effect as noble metal nanoparticles. With near infrared laser irradiation of 808 nm, the light energy can be converted into a large amount of heat energy. At the same time, energy can be transferred to the surrounding oxygen to generate singlet oxygen with very strong activity. Due to the ability of acetylcholine which can target to bacteria, Ach@RuNPs attached to the surface of bacteria, through the synergy of PTT and PDT, most of MDR bacteria can be killed. Subcutaneous abscess model in mice also demonstrated that the Ach@RuNPs has a good antibacterial activity with 808 nm near infrared laser irradiation, and with no appreciable abnormality in the major organs, in vivo. |
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