Research On Multifunctional Biomedical Nanoparticles Based On Transition Metal Coordination

The growing problem of bacterial resistance caused by the abuse of antibiotics is a serious challenge for the world.Therefore,the development of antibacterial therapies that do not rely on antibiotics has attracted much attention.Compared with traditional antibacterial therapies,antibacterial photothermal therapy（APTT）and antibacterial photodynamic therapy（APDT）are considered to be promising new therapies against super-resistant bacteria,because they have no fixed target and will not induce bacterial resistance.Therefore,two nano-scale antibacterial agents constructed by the coordination of transition metal iron and organic small molecules were designed,and their killing effect on drug-resistant bacteria were verified in this article.The first synergistic antimicrobial agent was mediated by APTT and antibiotics,FeTGNPs system.The second was synergistic antimicrobial agent was mediated by APDT and low-temperature APTT,Fe-TCPP@CS system.The main research contents were as follows:In order to make the clinically available antibiotics regain their killing effect on drug-resistant bacteria,we had introduced the emerging APTT.Based on the interdependent synergy between APTT and antibiotics,and the photothermal effect could improve drug sensitivity,the goal of high-efficiency sterilization under low antibiotic dosage could be achieved.To achieve this goal,we designed nanoparticles（FeTGNPs）composed of ferric iron(Fe³⁺),tannins（TA）and gatifloxacin（GAT）.FeTGNPs were prepared directly in aqueous solution by a one-step synthesis method.The successful construction of FeTGNPs was verified through a series of characterization methods.The successful loading of GAT and the excellent photothermal performance of FeTGNPs were verified.The antibacterial experiments showed that the synergistic effect of antibiotics and APTT could effectively kill drug-resistant bacteria.Antibacterial effect was much better than equivalent antibiotics.In order to completely eliminate the dependence on antibiotics and reduce the thermal damage to normal tissues caused by high heat,the emerging APDT and cationic polymer chitosan（CS）were introduced.It was mainly based on the interdependent synergy between APDT and low-temperature APTT,and the electrostatic targeting effect of positively charged CS on the bacterial outer membrane to compensate for the limitations of FeTGNPs system.The porphyrin（TCPP）was chosen as the photosensitizer and coordinated with the iron cluster（Fe₃O）in DMF to obtain Fe-TCPP,but the product had poor dispersion and showed a clustered cluster form.Therefore,CS was further introduced to modify it to obtain Fe-TCPP@CS.The dispersibility and stability were improved and the zeta-potential also changed from negative to positive.It was evaluated that Fe-TCPP@CS had good photodynamic and photothermal performance by using ROS probes,thermocouple and thermal infrared imager.Finally,the antibacterial experiments verified the effective killing effect of Fe-TCPP@CS on S.aureus,E.coli and drug-resistant bacteria under light conditions.