Design,Preparation And Bioimaging Application Of Near-infrared Ⅱ Nanoprobes

BackgroundThe near-infrared window with a wavelength between 1000 and 1700 nm,commonly known as the "second near-infrared(NIR-Ⅱ)window",has rapidly become a very attractive optical area for biological imaging.Compared with conventional imaging in the visible region of 400-700 nm and the first near-infrared(NIR-Ⅰ)window between 700-1000 nm,NIR-Ⅱ biological imaging has many advantages,including higher spatial resolution,deeper penetration depth,lower optical absorption and scattering from organisms,and the minimum fluorescence of tissue itself.Some NIR-Ⅱ contrast medium showed better performance than the clinically approved NIR-Ⅰ drugs.Therefore,NIR-Ⅱ has great potential in preclinical research and clinical application,and its biological imaging has been explored more and more.Lead sulfide(PbS)quantum dots(QDs)have attracted much attention over the years for optical and optoelectronic applications owing to their narrow bandgap and larger Bohr’s radii with respect to other QDs.The emission covering the entire NIR-Ⅱwindow makes it a very promising candidate material for live imaging.In this thesis,based on PBS QDs,two nanoprobes for bone imaging as well as tumor real-time imaging were constructed,respectively.Using these two probes in corresponding models for noninvasive real-time monitoring of bone marrow tissue-specific diagnostics,tumor drug delivery,and therapeutic processes at the live level,we expand the arsenal of tools for damage repair process monitoring with a view to reserve strength for NIR-Ⅱ bioimaging in preclinical studies and clinical applications.Objective1.Based on PbS QDs,a surface rich carboxyl nanoprobe was synthesized and its application in high-resolution bone marrow imaging in vivo was explored.2.Based on PbS QDs,a fluoropolymer coated DNA nanoclews for real-time imaging of oligonucleotide delivery and near-infrared light activation for anti-tumor angiogenesis was developed.Methods1.To improve the stability of PbS,a CdS shell layer is wrapped around the core of PbS.The CSQDs are transferred from the oil phase to the water phase using oil amine grafted polyacrylic acid(OPA),resulting in a surface rich carboxy group nanoprobe CSQDs OPA.Due to the existence of CdS shell,the probe maintains the high fluorescence performance of PbS core.Then the size,morphology and fluorescence characteristics of the synthesized nanoprobe were characterized,and its biocompatibility and bone imaging ability in mice were explored.2.DNA nanowires were synthesized by rolling circle amplification(RCA),and then modified with double bonds on the surface.The fluorinated amphoteric monomers were polymerized in situ to coat the polymer on the surface of DNA nanoclews.In the polymerization process,CSQDs were incorporated to finally synthesize fluorine-containing DNA nanoclews(FNCs)with real-time imaging of oligonucleotide delivery process and near-infrared light activation to inhibit tumor angiogenesis.Resultsl.The synthesized CSQDs-OPA nanoprobe has uniform size and stable performance.In vitro experiments showed that CSQDs-OPA had good biocompatibility.Injecting CSQDs-OPA nanoprobe into mice through the tail vein,non-invasive whole-body bone imaging of mice can be achieved in a short time to monitor bone-related abnormalities.2.FNCs carriers can deliver oligonucleotides to tumor cells through blood circulation.The photothermal effect of CSQDs under NIR light irradiation promotes the dissociation of hydrogen bonds,resulting in the shedding of fluoropolymers and the simultaneous release of loaded oligonucleotides(Anti21).Anti21 can silence miR-21,inhibit the secretion of vascular endothelial growth factor(VEGF)in tumor,inhibit angiogenesis,and ultimately lead to tumor ablation.At the same time,using NIR-Ⅱ imaging,we have achieved non-invasive volume imaging of gene vectors entering tumor cells from blood circulation.ConclusionBased on PbS QDs,this project has successfully constructed two NIR-Ⅱnanoprobes for bone marrow imaging and tumor diagnosis and treatment,which are respectively used for bone imaging and tumor diagnosis and treatment.Through in vitro and in vivo experiments,these two NIR-Ⅱ nanoprobes can effectively conduct bone imaging and tumor diagnosis and treatment,expand the tool library of bone and tumor imaging,and provide strong support for the development of NIR-Ⅱnanoprobes.