Construction And Application Of Near Infrared Laser Induced Nanocomposites With Multiple Antibacterial Properties

Bacterial infection is one of the most common diseases threatening human health.Antibiotics have made tremendous contributions to the treatment of bacterial infections.However,the extensive use and misuse of antibiotics have induced the emergence of drug-resistant strains,even superbugs.In addition,with the extensive use of biomaterials,biomaterial centered infections(BCI)remain as an unresolved problem,due to bacteria adhesion and proliferation on the surface eventually forming matured self-protective biofilms.Compared with free bacteria,the presence of biofilm enhanced the antibiotic resistance of bacteria in biofilm by 10~1000 times.Near infrared light(NIR)has good penetration ability to biological tissues and little harm to healthy tissues.In recent years,photothermal therapy based on near-infrared radiation has been widely used to fight against drug-resistant bacteria infection or eradicate biofilm due to its special physical sterilization mechanism.Based on the near infrared stimulated thermosensitive microgel,we have carried out some basic research in two aspects: killing the drug-resistant bacteria and eliminating the matured biofilms,and preventing bacteria from forming biofilms on the surface of biomaterials.Specifically,(A)the nanocomposites with both photothermal and antibiotic based chemical antibacterial activities were constructed to kill drug-resistant planktonic bacteria and eliminate matured biofilms.(B)The nanocomposites with photothermal and temperature sensitive effects were used as the basic elements to construct a multifunctional surface with the function of antifouling,sterilization and self-cleaning activities,which could prevent bacteria from adhering on the biomaterials and further forming matured biofilms.(1)In order to improve the penetration into deep bacterial biofilms of nanomaterials,gold nanorods(GNR)were prepared and encapsulated into a thermosensitive microgel(poly(N-isopropyl acrylamide)(PNIPAM)),which resulted a novel core-shell nanocomposites(GNR@P(NIPAM-AA-MAA))with surface charge transformable activities,NIR induced local hyperthermia and thermal responsive properties.Furthermore,a model antibiotic(ciprofloxacin,CIP)was encapsulated into the polymer shell of the nanocomposites,which can be released in respond to NIR.The CIP loaded nanocomposites are denoted as GNR@P(NIPAM-AA-MAA)-CIP.The nanocomposites show negative surface charge in normal physiological environment(pH=7.4),which can facilitate long blood circulation.When reaching the site of bacterial infections which are characterized as acidic microenvironment(p H=5.5),the nanocomposites present net positive surface charge as a result of protonation of N-allylmethylamine(MAA).The positive surface charge facilitates both enhanced electrostatic interaction between the nanocomposites and bacteria cells and their deep penetration into matured biofilms.In addition,the photothermal effect stimulated by NIR makes the nanocomposites shrink in volume,which further increases the penetration of the biofilm and releases ciprofloxacin,realizing the synergistic antibacterial effect of hyperthermia and chemical therapy.The results show that the nanocomposites have excellent killing efficiency against drug-resistant bacteria and the ability to eliminate biofilm.(2)In order to prevent bacteria from adhering to the surface of materials and forming matured biofilms,temperature responsive nanocomposites(TRNC)and none responsive nanocomposites(NRNC)were used as the basic elements to modify the surface of biomaterials.NRNC was composed of polyethylene glycol(PEG)shell and gold nanorods core.TRNC has the function of deformation caused by temperature,composed of PNIPAM shell and gold nanorods core.Therefore,TRNC coating has the function of deformation caused by NIR,which results in the release of bacteria killed by hyperthermia,self-cleaning.When a small number of bacteria were adsorbed on the surface of the material,and even mature biofilm was formed,TRNC coating and NRNC coating showed good photothermal disinfection activities to drug-resistant bacteria and killing performance against matured biofilm.TRNC coating could release dead bacteria actively through surface movement induced by thermal induced reversible volume change of TRNC,after several times of intermittent with NIR irradiation.Therefore,TRNC coating is a kind of multifunctional coating with antifouling,biocidal and self-cleaning properties,which can be used for surface modification of biomedical materials to prevent biofilm induced infections.