Synthesis Of Aloe-Emodin/Carbon Nanoparticle Hybrid Gels And Its Application In The Antimicrobial Synergistic Therapy

Background:In the late 20th century,with the emergence of drug-resistant strains,conventional antibiotics had become increasingly unable to meet the needs of clinical anti-infective treatment.Wounds and soft tissue infections caused by microorganisms,especially Staphylococcus aureus,were one of the most common types of infections today,posing a serious threat to human health.Therefore,it was an urgent need to explore an antibacterial dressing with excellent antibacterial properties and good biosafety for wound treatment.In many wound dressings,hydrogels could efficiently adsorb water molecules due to their own three-dimensional network structure to maintain the moist environment of the wound.It was also able to absorb tissue exudates,allowing oxygen to penetrate and inhibit the growth of microorganisms,and promote wound healing.These properties had made the application of hydrogels in the field of antibacterial more and more attention.So far,antibacterial gels mainly include two types:(1)The gel was constructed using the polymer material with antibacterial property as matrix;(2)The antibiotic was loaded into the network structure of the hydrogel by embedding,and it also exerted its effects through the release of antibiotics.However,actual infections tend to be more complex,such as infections and cross-contamination of resistant bacteria.At this time,a single anti-infective treatment was often difficult to meet the clinical needs,so it was particularly important to develop new type of antibacterial gel dressing that was versatile and effective against drug-resistant bacteria.In this paper,a polymer hydrogel with natural antibiotic(aloe emodin,AE)and carbon nanospheres was constructed,and its physicochemical properties and antibacterial properties were studied in detail.The results showed that carbon nanospheres could efficiently convert light energy into heat energy and killed bacteria under the illumination of near-infrared light.In addition,near-infrared light could induce carbon spheres to generate a large amount of active oxygen,and cooperate with light heat to kill bacteria in a short time.At the same time,the slow release of AE in the gel could be continuously sterilized after laser irradiation.These two instantaneous and long-lasting antibacterial methods could work synergistically to effectively inhibit the growth of harmful microorganisms,and had good killing ability against Gram-positive bacteria,Gram-negative bacteria and resistant bacteria.Animal wound infection model test results also showed that the hybrid gel could also promote wound healing.Purpose:At present,the increasing resistance of bacteria had made it imperative to develop new antibacterial agents that were highly effective in sterilization,environmentally friendly,and avoiding drug resistance.In this paper,the mixed hydrogel loaded with carbon spheres and aloe-emodin was constructed by polymerization.Under the induction of near-infrared light,the gel could generate heat by photothermal conversion to kill bacteria in a short time.When accompanied by heat generation,it could also generate high concentration of free radicals to impair cell membrane integrity and kill bacteria.The aloe-emodin inside the loaded gel was slowly released from the hydrogel and acted as continuous antibacterial after the laser was turned off.The combination of these two antibacterial methods could significantly improve the antibacterial effect of the gel system,effectively treat bacterial infections,and promote wound healing·Method:Chapter 1 Mechanistic Insight into the Light-Irradiated Carbon Capsules as an Antibacterial AgentIn this chapter,nitrogen-doped carbon capsules(N-CCs)were synthesized first synthesized,and then polyethylene glycol was modified on the surface to construct PEG-N-CCs.The physical and chemical properties of the carbon sphere were analyzed by various detection methods,including composition,size distribution,structure and photothermal conversion performance.Subsequently,the antibacterial activity of PEG-N-CCs was studied,and its antibacterial mechanism was studied,including the determination of the temperature inside the bacteria,the detection of the level of reactive oxygen species,the observation of bacterial morphology and the situation of nucleic acid cleavage in bacteria.The ability of PEG-N-CCs to remove and inhibit bacterial biofilms was explored.Chapter 2 Aloe-Emodin/Carbon Nanoparticle Hybrid Gels with Light-Induced and Long-Term Antibacterial ActivityBased on the first chapter of the thesis,this chapter chose polydimethylaminoethyl methacrylate(PDMAEMA)as the matrix of hydrogel.Polyethylene glycol modified carbon nanoparticle(PEG-N-CCs)and aloe-emodin(AE)were co-incorporated into the hydrogel to form AE/PEG-N-CCs hybrid gel.The physicochemical properties of hydrogels were also characterized by a variety of detection methods,including in vitro stability,structural characteristics,rheological properties,release of aloe-emodin,biocompatibility and photothermal properties.The long-term and short-term antibacterial activities of AE/PEG-N-CCs hybrid gel were discussed and the mechanism was studied.Finally,the mouse wound infection model was constructed to investigate the effect of wound healing.Results:Chapter 1:The PEG-N-CCs nanoparticles prepared in this chapter were uniform in shape,with the particle size was about 170 nm and the wall thickness was about 8 nm.The modification of polyethylene glycol greatly improved the water solubility,stability and dispersibility of the carbon nanoparticles.The results of bacteriostatic experiments showed that PEG-N-CCs had good antibacterial effects against Gram-negative bacteria,Gram-positive bacteria and resistant bacteria under near-infrared light irradiation.The inhibition mechanism was mainly through the conversion of light energy into heat energy by the carbon sphere under the irradiation of the laser.At the same time,higher levels of free radicals were generated,resulting in bacterial membrane destruction,intracellular matrix leakage,and rapid death of bacteria.In addition,PEG-N-CCs could destroy existing biofilms and prevent the formation of new biofilms with the near-infrared light,which could be used as an effective antibacterial agent.Chapter 2:The AE/PEG-N-CCs hybrid gel prepared in this chapter,had good shear resistance and self-healing properties and was suitable for wound coating.On the one hand,the PEG-N-CCs inside the gel could convert light energy into heat energy for rapid sterilization in a short period of time.On the other hand,the aloe-emodin inside the gel exerted long-term bacteriostatic effect through slow release to compensate for the short-term antibacterial process,once the light source was turned off,its antibacterial process would stop.Compared with monotherapy,the two antibacterial methods worked together to make the gel exhibit superior antibacterial effects.At the same time,animal wound healing experiments showed that AE/PEG-N-CCs hydrogel could effectively treat wound infection and promote wound healing.