Research On The Photodynamic Device Of Cyanobacterial Light Triggered By Near-infrared Light And Its Application In Antibacterial Therapy

Periodontitis is one of the most prevalent chronic inflammatory diseases in the world,which is a chronic inflammation of periodontal support tissue caused by plaque microorganisms,if not controlled in time,the inflammation will gradually spread to the deeper depths,eventually leading to loosening or even loss of teeth.At the same time,a large number of studies have confirmed that periodontal disease is also closely related to many systemic diseases of the whole body.Therefore,how to treat periodontitis safely and effectively is a very critical issue.At present,most of the clinically use mechanical therapy supplemented with antibacterial drugs to treat periodontitis,but the complex structural characteristics of periodontal pockets make it difficult to achieve thorough debridement and sterilization.Long-term use of antibiotics can also lead to the development of bacterial resistance.Therefore,photoresponsive antibacterial photodynamic synergistic therapy has a wide range of applications in antimicrobial therapy due to its advantages of high selectivity,wide antibacterial spectrum,few side effects and less resistance to antimicrobial therapy.However,there are still some tricky problems in the antibacterial synergistic treatment of periodontal inflammation:(1)oxygen is one of the three basic elements in antimicrobial photodynamic therapy(aPDT),but the periodontal pocket formed by periodontitis is a severely hypoxic microenvironment,which greatly weakens the effect of photosensitizer-mediated antibacterial photodynamic therapy.At the same time,the main pathogenic bacteria of periodontitis are mostly anaerobic bacteria,and when the oxygen consumption is continuously consumed during aPDT treatment,it will further aggravate the hypoxia of the periodontal pocket microenvironment,which is not conducive to the inhibition of the main periodontal pathogenic bacteria.(2)Periodontal pathogenic bacteria tend to form a relatively dense plaque biofilm on the surface of periodontal tissue,and when the biofilm is dissipated at high temperature with photothermal therapy(PTT),it is easy to cause thermal damage to the surrounding periodontal tissue due to excessive temperature.At the same time,most of the existing photothermal agents are inorganic materials or carbon-based materials,and the biological safety needs to be further improved.Therefore,it is of great clinical significance to explore a safe and efficient self-oxygen device excited by near-infared light(NIR)to combat periodontal pathogenic bacteria.In this study,a NIR-triggered cyanobacterial photodynamic device was designed,which can be used as a natural biothermal agent and oxygen supply carrier at the same time,on the one hand,because of its own active characteristics,the temperature can be controlled within the safe range of the human body to protect the surrounding tissues from thermal damage,and at the same time improve the biological safety of the photothermal agent.On the other hand,it also improves the microenvironment of periodontal pockets and the problem of hypoxia in the treatment of aPDT,further improves the antibacterial treatment effect of aPDT in vivo/external,and provides a new idea for the treatment of periodontitis.The specific research content is as follows:(1)Two different luminescent upconversion nanoparticles were prepared by conventional high-temperature co-precipitation method,and one particle provided a light source for the photosynthesis of the whole device in vivo.Another particle is used to excite the photosensitizer dihydroporphyrin e6(Chlorin e6,Ce6),which combined to make the whole device have a good antibacterial therapeutic effect.To further optimize the water solubility and biocompatibility of the nanomaterials,we used biphilic silanes to modify the two particles prepared.Finally,the two modified particles are loaded into the cyanobacteria in the optimal proportion to form a NIR-excited cyanobacterial photodynamic device.(2)When the device was irradiated by NIR at 980 nm,the non-photochemical quenching mechanism of cyanobacteria was able to convert light energy into heat,thereby realizing PTT to eliminate the stubborn plaque biofilm formed on the surface of periodontal tissue.At the same time,the photosynthesis of cyanobacteria will continuously produce oxygen,and the introduced Ce6 can produce a large amount of singlet oxygen after being excited.The device not only effectively alleviates the problem of hypoxia in the treatment,but also plays a good aPDT/PTT synergistic antibacterial treatment effect.(3)In vitro,the synergistic antibacterial performance of aPDT/PTT was evaluated in vitro,and in the experiment,we selected Porphyromonas gingivalis(P.gingivalis)and Fusobacterium nucleatum(F.nucleatum),two bacteria associated with periodontal disease.Animal-level antibacterial experiments were carried out on the periodontitis model of rats,which verified that the prepared cyanobacterial photodynamic device had stable oxygen supply function and good synergistic antibacterial treatment effect.