Study On Multi-modal Nanoprobe For Tracing Bacteria Based On Hollow Mesoporous Silica

The complexity of diagnosis and treatment of knee joint related infectious diseases is an important problem for clinicians.At present,the gold standard for clinical diagnosis of knee joint related infectious diseases depends on the bacterial culture and identification of the infected local tissues,but the clinical diagnosis of knee joint related infection is far from enough.In order to develop effective means of bacterial infection,it also depends on the tracing of bacteria in the body,which will help surgeons provide important theoretical basis for the surgical treatment of infectious diseases.The sensitivity and accuracy of single-mode imaging in identifying pathological tissues are not high,and the nanoprobe integrated with multi-mode imaging is more helpful to improve the effect of early localization diagnosis of bacterial tracers in infectious diseases.With the advantages of hollow mesoporous silica nanoparticles(HMSN)material,such as good biocompatibility,easy to be modified by organic groups,high specific surface area and pore volume,and the hydrolysis and dehydrogenation of active molecule ammonia borane(AB),the synthesized material can form microbubbles locally under ultrasound(US)and X-ray irradiation,can reduce CT density in local areas,and enhance local ultrasound and X-ray imaging.Superparamagnetic Fe₃O₄ nanoparticles can enhance the relaxation time of T2 under magnetic resonance imaging.Based on this,a multifunctional nanoprobe is prepared(Fe₃O₄@HMSN-AB),which is helpful to improve the sensitivity and specificity of bacterial localization diagnosis of infectious diseases.The research results are as follows:In the first part,hollow mesoporous silica spheres were synthesized by template method,and their surfaces were functionalized and loaded with ammonia borane to prepare nanoprobe.Mesoporous silica(HMSN and HMSN-T)with different pore sizes and hollow structures were selectively etched with silica as a hard template.The materials were obtained by grafting amino groups(-NH₂)and targeted bacterial molecules(-COOH-PEG-UBI_29-41)on their surfaces and ab loading through the substitution reaction between groups.The dehydrogenation results showed that the materials had US/CT imaging potential.Taking HMSN-T synthesized with pore enlarging agent as the basic element,the influencing factors of AB loading were studied.The results showed that the material had high repeatability and high AB loading(12.14 wt%),and the AB loading was related to the type of solvent and the ratio of material to liquid.The atomic ratio of element B showed that HMSN-T with larger pore sizes(4.69 nm and 5.88 nm)is more conducive to the loading of ammonia borane.The hydrogen release of the materials was further observed.The results showed that compared with HMSN,HT-U-AB series materials had higher sensitivity to p H environment,which was more conducive to improve the accuracy of early diagnosis of knee synovium.In the second part,Fe₃O₄ synthesized by pyrolysis and its surface modification were combined with HMSN to obtain a multifunctional nanoprobe of magnetic hollow mesoporous silica.Based on the results of the first part,combined with the characteristics of superparamagnetic nanoparticles enhanced MRI,this chapter combines magnetic nanoparticles and synthetic multimode imaging nanoprobes targeting bacteria Fe₃O₄@HMSN-AB.Fe₃O₄ nanoparticles synthesized by high temperature thermal decomposition have hydrophobic oleamine molecules on the surface,which can not be directly used for infection diagnosis.After coating its surface to obtain stable and small particle size,the obtained Fe₃O₄@Si O₂ nanoparticles have the potential of MR imaging,and further synthesized with hollow structure Fe₃O₄@HMSN.After bacterial targeting modification and AB molecular loading,a targeted bacterial material with multimodal imaging was obtained.The results showed that the loading amount of AB was high(13.54 wt%),the dehydrogenation rate of the material was fast,and the response to acidic environment was fast.It was used to enhance US/CT/MRI,which was more helpful to improve the imaging accuracy.According to the above research,the subject obtains HT-U-AB with improved imaging accuracy,which is prepared by combining magnetic Fe₃O₄,the Fe₃O₄@HMSN-AB has the characteristics of US/CT/MRI the third mock examination imaging,and has the application potential to improve the accuracy of early diagnosis of knee synovium.Finally,the application potential of materials based on hollow mesoporous silica and ammonia borane is summarized and prospected in the future.