Diagnosis And Treatment Of Bacterial Inflammation Enabled Through Functional Silicon Nanoparticles-Based Probes

During past decades,public health is overwhelmed by bacterial infections,especially for drug-resistant bacterial infections.To date,a promising concept,that is optical imaging-guided treatment of bacterial infections,fuels urgent demands for the fabrication of novel multifunctional theranostic probes,which allow simultaneous detection and treatment of early-stage bacterial infections.The development of nanotechnology provides new avenues for designing nanomaterial s-based multifunctional probes for myriad biomedical applications.On the other hand,in recent years,fluorescent silicon nanoparticles(SiNPs)-based probes have been extensively exploited for bioimaging,biosensor,as well as disease diagnosis and treatment,etc.In our thesis,we develop a kind of functional probes based on the fluorescent SiNPs,which is available for bacterial detection and antibacterial application.The details are as follows,Firstly,we give an introduction of the synthesis of fluorescent SiNPs,and the progress in bacterial detection and antibacterial application in vitro.The developed theranostic probes are made of fluorescent SiNPs prepared through photochemical synthesis,followed by surface modification with vancomycin through chemical coupling reaction(SiNPs-Van).The resultant fluorescent SiNPs-Van display excellent photostability,whose fluorescence signals keep stable under 40-min continual laser irradiation;in comparison,the fluorescence from Hoechst,known as a conventional fluorescent organic dye,rapidly vanishes after 5-min continuous irradiation.Besides,the SiNPs-based probes are able to kill Gram-positive bacteria,and the corresponding minimum inhibitory concentration(MIC)of SiNPs-Van is 0.5 μg/mL;in contrast,the MIC of pure-vancomycin is 1 Cytotoxicity assay is further carried out to evaluate cytotoxicity of SiNPs-Van.In our experiment,MDA-MB-231 cancer cells and HREC normal cells are incubated with the SiNPs-Van with different concentrations for 24 h,respectively.The cell viability of both cellular lines remains over 95%,demonstrating negligible cytotoxicity of the SiNPs-Van.The developed probes can be further used for the quantification of Gram-positive bacteria in the range of 106 to 109 CFU/mL,which is based on the linear relationship between the logarithmic bacterial concentrations and corresponding change of photoluminescence intensity.Secondly,the SiNPs-Van is further employed for in vivo bacterial detection and antibacterial application.We reveal that the fluorescence signal intensities are reduced along with the decrease of the numbers of bacteria in the infection sites,providing a visualized way to evaluate the efficacy of antimicrobial therapy for the S.aureus infection.The resultant SiNPs-Van features the superior antimicrobial activity(92.5%)to that of free Van(76.5%),since the local concentration of vancomycin on the bacterial surface is higher than that of free vancomycin.Furthermore,the in vivo biodistribution of the probes is evaluated.We find that,besides high accumulation in the infected sites,bright fluorescence is also observed in kidney while feeble fluorescence is observed in other organs at 6-h postinjection;the fluorescence in kidney is undetectable at 8 days postinjection,indicating that SiNPs-Van is eliminated from the mice through renal clearance due to their small sizes.To be summarized,in this thesis,we employ the SiNPs featuring favorable biocompatibility and unique optical properties for constructing a kind of high-performance probes,which are efficacy for simultaneous long-term fluorescence imaging of bacteria infections and destruction of bacteria.