The Applications Of Near-infrared Quantum Dots In Biomedical Analysis And Biological Imaging

As novel fluorescence nanoparticles, near-infrared quantum dots (NIR QDs) havebeen extensive attention from researchers in the field of bioimaging and bioassayapplications. The fluorescence emission wavelength of NIR QDs are usually innear-infrared region between650-900nm, for bioimaging and bioassay is veryresearch value. NIR QDs not only retain all of the advantages of visible quantum dots,but also have their own unique optical features. More importantly, NIR QDs havestronger penetration ability, which can effectively avoid the absorbance and autofluorescence from the tissues. Therefore, the NIR QDs have been widely used inmany fields such as biomedicine.Nonetheless, NIR QDs are still facing some unsolved problems such ascytotoxicity of heavy metal ions in the NIR QDs and organic groups of the surface ofNIR QDs, toxicity in the process of organic synthesis. Most of NIR QDs aresynthesized via an organometallic precursor route in an organic solvent that ishazardous to the environment and to the health of the people.Thus, the developmentof less toxic and more environmentally friendly ternary NIR QDs materials hasattracted considerable attentionI-III-VI type CuInS2QDs which is a kind of NIR QDs are synthesized byhydrothermal synthesis. CuInS2QDs do not include heavy metals such as cadmium,mercury and lead etc., could effectivey reduce the toxicity of conventional NIR QDsand improve a biocompatible. This method make it more suitable for biologicalapplications. In this paper, we focus on the application of water-soluble CuInS2NIRQDs in a wide range of biomedical assays and imaging of tumour cells anddiagnosing cancer, summarized as follows:In the chapter1, we described the properties of QDs and recent developments inthe synthesis and biomedical application of QDs. And we introduced some recent reports about the preparation and bioimaging application of NIR QDs.Finally, weprovided the significance and contents of this dissertation.In chapter2, near-infrared fluorescent CuInS2QDs@SiO2nanobeads wereprepared and used as fluorescent nanoprobes for prostate cancer cells imaging. Thecore-shell CuInS2QDs@SiO2nanobeads with controllable particle sizes weresynthesized via a reverse microemulsion method. Further surface modifications wereperformed for grafting amino groups on the surface of the near-infrared CuInS2QDs@SiO2nanobeads. For prostate cancer cell imaging, anti-PSCA antibody wasconjugated to the near-infrared CuInS2QDs@SiO2nanobeads to prepare theanti-PSCA-QDs@SiO2nanoprobe. The specific binding of the antibody conjugatedCuInS2QDs@SiO2nanobeads to the surface of human prostate cancer cells (PC-3M)was confirmed by fluorescence microscopy. MTT assay and fluorescence microscopyimages showed that anti-PSCA-conjugated NIR CuInS2QDs@SiO2nanoprobe wasnon-toxic nanoprobe and had high-specificity in cell imaging. CuInS2QDs@SiO2nanoprobe as an efficient near-infrared imaging nanoprobe could be used for targetimaging, biological assays and early diagnosis of cancer.In chapter3, a novel daunorubicin (DNR)-loaded MUC1aptamer-near infraredCuInS2quantum dot (DNR-MUC1-QDs) conjugates were developed, which can beused as a targeted cancer imaging and sensing system. After the CuInS2QDsconjugated with the MUC1aptamer-(CGA)7, DNR can intercalate into thedouble-stranded CG sequence of the MUC1-QDs. We evaluated the capacity ofMUC1-CuInS2QDs for delivering DNR to cancer cells in vitro, and its bindingaffinity to MUC1-positive and MUC1-negative cells. This novel aptamerfunctionalized QDs bio-nano-system can not only deliver DNR to the targetedprostate cancer cells, but also can sense DNR by the change of photoluminescenceintensity of CuInS2QDs, which concurrently images the cancer cells. We demonstratethe specificity and sensitivity of this DNR-MUC1-QDs probe as a cancer cell imaging,therapy and sensing system in vitro. In chapter4, we developed a near-infrared Mercaptopropionic acid(MPA)-capped CuInS2quantum dot (QDs) fluorescence probe for the detection ofacid phosphatases (ACP), which is an important biomarker and indication of prostatecancer. The fluorescence of CuInS2QDs could be quenched by Cu2+and then theaddition of adenosine-5′-triphosphate (ATP) could effectively turn on the quenchedfluorescence due to the strong interaction between Cu2+and ATP. The ACP couldcatalyze the hydrolysis of ATP that would disassemble the complex of Cu2+–ATP.Therefore, the recovered fluorescence could be quenched again by the addition ofACP. In our method, the limit of detection (LOD) is quite low for ACP detection insolution. By using the CuInS2QDs fluorescence probe, we have successfullyperformed in vitro imaging of human prostate cancer cells.In chapter5, we developed a simple near-infrared fluorescence assay usingthrombin binding aptamer (TBA) and Zn2+-activating CuInS2quantum dots (QDs) forthe highly selective and sensitive detection of thrombin. The fluorescence ofZn2+-activating CuInS2QDs could be effectively quenched by TBA via thephotoinduced electron transfer process. When thrombin was added, the TBA wasinduced to form G-quadruplexes which bound with thrombin due to the specificinteractions, the Zn2+-activating CuInS2QDs was released and the fluorescenceintensity of the system was restored. The proposed approach provides a simple andfast responding procedure, and the ability of this method to detect thrombin atpicomolar levels holds great potential in the diagnosis of diseases associated withcoagulation abnormalities and cancers.