| Multi-drug resistant(MDR)bacteria pose a major threat to public health due to the rapid evolution of pathogenic bacteria and the severe misuse of antibiotics.It is predicted that this drug-resistant infection will become the number one cause of human death within thirty years.With the successive failure of old antibiotics and the shortening effective cycles of new antibiotics,the ability of humans to control infections through drugs is further limited.The rapid development of nanotechnology offers a potential alternative to anti-infection therapy.Compared with conventional antibiotics,nanomaterials are less likely to induce bacterial resistance because they have different antibacterial mechanisms.In the past decade,a large number of antimicrobial nanomaterials have been developed to combat pathogens.However,the complexity of the actual environment(hospitals,clinical infections,food industry,etc.)has put new demands on the antimicrobial efficiency,antimicrobial durability,biocompatibility,and multifunctionality of antimicrobial materials.Therefore,there is an urgent need to develop novel antibacterial nanomaterials by various feasible chemical or physical approaches to meet the new requirements for the development of the antibacterial field.(+)-Borneol is a bicyclic monoterpene natural membrane-active antimicrobial agent,which has been widely used in antimicrobial materials due to its unique cell membrane disruption mechanism and chiral steric structure.However,its poor water solubility severely limits its antimicrobial efficiency in practical applications and reduces the economic value as an antimicrobial agent.This thesis focused on three pain points of current antimicrobial materials,namely,poor antimicrobial efficiency,non-durable antimicrobial activity and significant side effects.Inspired by the cationic and hydrophobic structures of antimicrobial peptides(AMPs),the hydrophilic and antimicrobial performance of the(+)-borneol were optimized firstly.Then,based on the behavioral and surface properties of bacteria,we systematically explored the antibacterial activity,antibacterial law and mechanism of hydrophilic borneol-based polymers(BPs)at two application levels: interfacial antibacterial and solution antibacterial,using cotton fabric and two-dimensional MXene as composite carriers,respectively.This work aims to provide theoretical basis and technical support for the high value utilization of borneol and its application in antibacterial field.The main research contents and conclusions of this paper are as follows:(1)Synthesis and antibacterial properties of borneol-based polymersTo address the problem of low antibacterial efficiency of(+)-borneol,inspired by the cationic and hydrophobic structures of AMPs,hydrophilic borneol-based polymers(Borneol-PDMAEMA,BP)with different molecular weights were synthesized by atom transfer radical polymerization(ATRP)technique using(+)-borneol and dimethylaminoethyl methacrylate(DMAEMA)as raw materials.The relationship between the structure and antibacterial properties of BP was investigated to screen the optimal structure BP1 and elucidate the antibacterial mechanism of BP.Finally,the biocompatibility of BP was investigated by hemolysis test.It was shown that BP exhibited outstanding antibacterial ability against Gram-negative and Gram-positive bacteria,and even methicillin-resistant Staphylococcus aureus(MRSA),due to its excellent dispersion in water.The minimum bactericidal concentration(MBC)of BP1 was only 39 μg/m L against E.coli and 50 μg/m L against MRSA.Moreover,BP was not significantly toxic to mammalian erythrocytes.The study of the antibacterial mechanism of BP reveals that the membrane disruption mechanism of borneol is synergistic with the targeted attachment of protonated PDMAEMA to bacteria through electrostatic action,which ultimately leads to the disruption of bacterial cell membranes,leakage of contents,and intense intracellular oxidative stress(including oxidation of DNA,proteins,and lipids),thus ultimately inducing bacterial death.(2)Construction and antimicrobial activity of durable antimicrobial cotton fabrics functionalized with borneol-based polymersTo address the non-durable antimicrobial properties of current coating strategies,a simple and green approach for the construction of BP-functionalized non-leaching durable antimicrobial cotton fabric(BP@CF)with hydrophilic borneol-based polymers(BP)was proposed,and its potential for various biomedical antimicrobial interface applications was explored.First,a borneol-based block copolymer(BP-b-HM)was synthesized by ATRP in one step.Then,BP covalently anchored cotton fabric(BP@CF)was successfully prepared by a simple dip-coating-annealing treatment.Compared with commercially available antimicrobial cotton fabrics(AEM@CF),BP@CF could achieve rapid killing of E.coli within 2 h with long-lasting bacterial inhibition ability.The contact angle test results showed that the initial superhydrophobic nature of BP@CF(water contact angle of 150.2±7.2°)makes it liquid repellent and anti-adhesive in air;and when there is too much liquid or stays on the surface of the coating for a long time,it causes a shift in the free energy of the BP@CF coating surface,which activates the protonation of the PDMAEMA chain and further synergizes with the borneol group to achieve the killing of bacteria in liquids.Since the covalent anchoring mechanism of BP-b-HM is cross-linked with the hydroxyl group of the interface,thus making the construction method of this durable antibacterial interface with the potential to be applied to various biomedical antibacterial interfaces.(3)Preparation and antibacterial mechanism of borneol-based polymer functionalized two-dimensional MXene nanocomposite antibacterial agentTo address the high side effects of photothermal antimicrobial therapy,BPQ@2DM(BPM)was obtained by electrostatic assembly of quaternized borneol-based polymers(BPQ)with two-dimensional MXene(2DM)nanosheets.The successful preparation of BPM not only improved the stability and conferred pathogen-targeting of 2DM in the physiological environment,but also developed a novel low-temperature targeted photothermal antimicrobial therapy(BPM-mediated photothermal therapy).It was shown that this antimicrobial therapy achieved 99.999% bactericidal efficiency against MRSA at a safe temperature(≤40 ℃)in human tissues.This low-temperature targeted antibacterial mechanism can be attributed to the membrane-targeting ability of BPM to generate localized heat in situ in the bacterial cell wall in synergy with the photothermal effect.With this direct targeted heat transfer effect,the pathogenic bacteria are annihilated in situ with less macroscopic heat change in the system,avoiding the damage to adjacent normal tissues by conventional photothermal therapy.Moreover,BPM can achieve multi-modal synergistic sterilization by significantly boosting intracellular ROS levels and inhibiting ATP synthesis while disrupting cell membranes.In mice wound infection experiments,BPM,as an antibiotic-free agent,significantly reduced MRSA at the wound site and promoted rapid wound healing,which has great potential in the treatment of drug-resistant bacterial infections in vivo. |
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