Functionalization Of Rare Earth Nanoprobes For In Vivo NIR-Ⅱ Fluorescent Bioimaging And Therapy

Rare earth nanomaterials（RE NPs）have been constructed as promising nanoprobes for a variety of applications due to their tunable optical properties,photostability,and tissue penetration capabilities.These nanoparticles have been widely used in optical sensing,deep tissue and in vivo imaging,photoinduced drug release and photothermal therapy,etc.RE NPs have downshifting luminescence located in the Near-Infrared-Ⅱ regions（NIR-Ⅱ,1000-1700 nm）,which provides an excellent imaging window due to the low absorption and scattering in organisms and high imaging resolution.However,RE NPs have small absorption cross sections,generally low quantum yields,and lack responsive groups,which necessitates the combination of other recognition units to modulate their luminescence performance in optical sensing.In this thesis,we modulated the luminescence properties of RE NPs by small molecule,designed a bifunctional rare earth nanoplatform for diagnosis and treatment of methicillin-resistant Staphylococcus aureus（MRSA）infection and a NIR-Ⅱ imaging probe in acetaminophen（APAP）-induced liver injury model,respectively,to achieve NIR photocontrolled nitric oxide（NO）sterilization and NIR-Ⅱ fluorescence imaging in a mouse model.Chapter 1 OverviewThis chapter provides an overview of the current state of research on RE NPs,including synthesis,modification and sensitization.We summarizes their potential applications in biosensing imaging,optical therapy,and optogenetic.Finally,we briefly described the research significance and the research content of this thesis.Chapter 2 Construction of NIR-controlled dual-functional dye-sensitized rare earth nanoprobes for deep tissue imaging and sterilization research.In this chapter,we developed a bifunctional optical platform based on RE NPs,CS NPs-ZIF-8-CysNO-TPEO-820（CZND）.The loading of the near-infrared dye TPEO-820 and nitric oxide（NO）releasing small molecules was achieved by encapsulating ZIF-8 shell layer on rare earth nanoparticles（CS NPs）.In this system,the original dye sensitization strategy was improved by introducing the TPEO group on the NIR dye IR-820 to obtain the dye TPEO-820with high quantum yield,which led to the amplification of the dual emission of RE NPs and achieved excellent dye enhancement.The TPEO-820 sensitization enhances the UV emission of the RE NPs by two orders of magnitude,leading to the efficient controllable release of nitric oxide.Moreover,the NIR dye sensitization enables a 10-times enhancement in the downconversion emission and facilitates deep-tissue imaging of bacterial infections.In a mouse leg abscess model,the NIR-Ⅱ imaging efficiency after dye sensitization was approximately 3.6-fold higher than that without sensitization.Superior therapeutic efficacy was achieved at a relatively low power（0.5W/CM²）in a MRSA skin infection model,and wound healing was accelerated by approximately three days relative to the unsensitized group.The great potential of the CZND platform for in deep imaging and controlled bacterial therapy was demonstrated.Chapter 3 Construction of ratiometric NIR-Ⅱ luminescent rare-earth nanoprobes and applications for nitric oxide detectionIn this chapter,we constructed a near-infrared Ⅱ ratio fluorescent probe of nitric oxide based on RE NPs.Highly efficient NIR-Ⅱ emission under 980 nm and 808 nm excitation was achieved by the high doping of Ce and the double core-shell structure.Subsequently,the loading of NO-responsive small molecule CyNO was achieved by encapsulating the CSS surface with a mesoporous silica shell layer.The CyNO can respond to NO according to the photo-induced electron transfer（PET）,resulting in enhanced absorption at 800 nm.Since the absorption cross section of the small molecule is significantly higher than that of CSS,the absorption competition induced effect will cause the F_1550Em,808Exunder 808 nm excitation decreases gradually,while the fluorescence emission F_1550Em,980Exunder 980 nm excitation remains relatively stable.There was a linear relationship between the signal ratio of F_1550Em,808Exand F_1550Em,980Exwith the NO concentration in the range of 0-16μM.The limit of detection（LOD）of probe was calculated to be 0.18μM.Moreover,the probe was used for NO detection during drug-induced liver injury（DILI）,providing a new method for indicating the disease process of CILI.