Imaging And Treatment Of Bacterial Infection Based On Silica Nanocomposites

Purpose:Bacterial infections,especially the rapid emergence of drug-resistant bacterial infections,are posing mounting public health concerns,and causing an enormous medical and financial burden.For instance,methicillin-resistant Staphylococcus aureus?MRSA?,one of the main dreaded clinical pathogens,cause many fatal diseases such as sepsis and acute endocarditis.At present,bacterial infections are mainly detected by culturing of tissue biopsies or blood samples in the clinic,which is time-consuming and invasive.Therefore,it is of great importance to develop a method with the capability for rapid detection and treatment of bacterial infections in vivo.Method:In this thesis,silica nanoparticles?SiO₂ NPs?are firstly synthesized and then conjugated with Cypate and vancomycin?Van?via layer-by-layer assembly of polyelectrolytes to obtain the SiO₂-Cy-Van nanocomposites.The SiO₂-Cy-Van nanomaterials are characterized by transmission electron microscope?TEM?,UV-Vis spectrophotometer,fluorescence spectrometer,dynamic light scattering?DLS?.Subsequently,the unique capabilities of SiO₂-Cy-Van nanocomposites for in vitro activatable near-infrared fluorescence?NIRF?imaging and photothermal elimination of MRSA are investigated.Furthermore,the specificity and sensibility of SiO₂-Cy-Van nanocomposites for in vivo MRSA infection diagnosis as well as photothermal treatment,are systematically investigated.Results:?1?The SiO₂-Cy-Van nanocomposites have a regular and well-defined spherical structure with size of?72.7±3.2?nm,and their hydrodynamic size is?184.9?1.6?nm and the PDI is 0.136.In addition,the Si O₂-Cy-Van nanocomposites have good size stability,photo stability,photothermal conversion capability and low cytotoxicity.Moreover,the SiO₂-Cy-Van nanocomposites are non-fluorescent in aqueous environments due to the aggregation of hydrophobic Cypate dye on silica nanoparticles.?2?In vitro experimental results indicate that non-fluorescent SiO₂-Cy-Van nanocomposites can be partly activated by MRSA,and the concentration of conjugated Cypate has critical effect on the MRSA-activated fluorescence turn-on of SiO₂-Cy-Van nanocomposites.We demonstrate that MRSA can effectively pull out the vancomycin-modified polyelectrolyte-Cypate complexes from silica nanoparticles and draw onto their own surface,changing the state of Cypate from off?aggregation?to on?disaggregation?and leading to in vitro MRSA-activated NIRF imaging and photothermal elimination involving bacterial cell wall and membrane disruption.?3?In vivo experimental results indicate that the SiO₂-Cy-Van nanocomposites can be activated by MRSA in the infection site and realize rapid and long-term imaging when the nanocomposites are injected into the MRSA-infected mice through tail vein.Additionally,the SiO₂-Cy-Van nanocomposites show unique capability for the high-sensitivity diagnosis and excellent photothermal treatment of MRSA infection in vivo.Conclusion:In this thesis,the robust theranostic nanocomposites?SiO₂-Cy-Van?for in vivo MRSA infection are successfully prepared.The SiO₂-Cy-Van nanomaterials have good stability and photothermal conversion capability and the non-fluorescent nanomaterials can be activated by MRSA and the fluorescence partly turns on,realizing NIRF imaging and PTT of the MRSA-infected mice.By combining the MRSA-activated NIRF imaging and PTT,the SiO₂-Cy-Van nanocomposites can significantly increase the imaging sensibility by eliminating the background fluorescence and autofluorescence interference of tissues,showing great prospect in diagnosis and treatment of MRSA infection in clinical settings.