Construction Of Upconversion Luminescent Nanomaterials And Its Application In Biomimetic Imaging

Optical bioimaging offers a unique approach for visualizing morphological details in tissue with subcellular resolution by virtue of its highly sensitive and high-speed spatial analysis of cells. Upconversion luminescence (UCL) mechanism excludes both endogenous components and conventional fluorescent probes, and thus UCL imaging with upconversion emissive nanomaterials as labels would seem to be able to completely eliminate background fluorescence in bioimaging. However, the upconversion luminescence materials were limited by low quantum efficiency and absorption across section, poor water-soluble, difficult to function and so no.This thesis is focused on the above-mentioned problems, and composed of two parts as following:I. Rare-earth doped UCL nanomaterials for bioimaging1) NaLuF4as host matrix for enhance UCL and high-sensitivity bioimagingUCL nanocrystals based on β-NaLuF4as host material with bright UCL have been synthesized by thermal decomposition in the presence of oleylamine. Such (3-NaLuF4:Gd,Yb,Tm nanocrystals display bright UCL emission with QY of0.47±0.06%, reflecting that the hexagonal NaLuF4:Gd3+,Yb3+,Tm3+is an excellent nanomaterial for upconversion emission. Using such P-NaLuF4:Gd,Yb,Tm nanocrystal as a UCL probe, an excellent detection limit of50and1000nanocrystal-labeled cells was achieved for injection subcutaneously and intravenously, respectively. In particular, high contrast UCL imaging of a wholebody black mouse with penetration depth2cm was achieved.2) Super-molecular self-assembly strategy for improving the water-solubility of UCNPWe have successfully developed a simple and efficient approach to draw hydrophobic UCNPs into water by the self-assembly of a host (β-CD) and guest (Ad). Compared with the reported two-step synthetic strategies, this method provides simple post-treatment (only stirring or shaking are needed), rapid response time (<20s), and high conversion yield (>95%). Notably, the complex exhibited good capability for bioimaging owing to its low cytotoxicity and bright UCL. However, this method is rather specific to Ad-capped nanoparticles. We further developed a general, simple and environment-friendly strategy to convert hydrophobic UCNP into a hydrophilic form by the self-assembly of host (a-CD) and guest molecules (surface ligand OA). This method can be widely applied in improving the water-solubility of UCNP, whose surface ligand is OA, and provides a hydrophobic layer for loading hydrophobic material (such as dye or drug). This approach has several advantages over previously reported methods, which may open up new perspectives for a unique synthesis of hydrophilic and uniform nanoparticles as an ideal building block for multimodal bioimaging (UCL and PET) probe and drug-loading nanosystem.3) Rare-earth cation-assisted ligand assembly for constructing multi-modal probeA novel strategy for modifying the surface of upconversion nanophosphors has been developed, which imparts them with excellent upconversion luminescence properties, MR, radioactivity, targeted function, and water-and biocompatibility, thereby making these nanoparticles a potential candidate for multimodal bioimaging. The versatility of this surface modification approach for incorporating functional molecules and fabricating radioactive magneticupconversion nanophosphors has been demonstrated by means of cellular targeted imaging, MRI, in vivo upconversion luminescence imaging, and PET imaging, and the as-synthesized UCNPs obtained by rare-earth cation-assisted ligand assembly can indeed be applied as a trimodal probe. In particular, the strategy of introducing Gd3+by cation exchange supersedes previous methods of Gd3+-doping or using a host material containing Gd3+, since surface Gd3+ions are mainly responsible for the T1enhancement in MRI.4) Upconversion luminescence Hg2+probe for sensoring in living cellWe have demonstrated a highly selective water-soluble nanoprobe based on dye-assembled nanophosphors for upconversion luminescence sensing and bioimaging ofmercury ions. The chromophoric ruthenium complex N719, as a Hg2+-selective dye, was successfully assembled on the surface of UCNPs. This dye-assembled nanosystem of ratiometric upconversion luminescence can detect Hg2t in aqueous solution with high selectivity, a rapid response time (<10s), and with high sensitivity (detection limit of1.95ppb). Such detection limit of Hg2+is only1/10of that of pure complex N719in chromophoric sensing Hg2+and is lower than themaximum level (2ppb) of Hg2+in drinking water set by the United States EPA. Importantly, the nanoprobe has been shown to be capable of monitoring changes in the distribution of Hg2+in living cells by upconversion luminescence bioimaging.II Upconversion luminescence based on triplet-triplet annihilation (TTA) for bioimaging5) Blue-emissive emission TTA-UCL nanoparticles for bioimaing in vivowater-soluble nanoparticles showing triplettriplet annihilation-based upconversion luminescence were successfully prepared by loading sensitizer (PdOEP) and annihilator (DPA) into silica nanoparticles. The upconversion luminescence quantum yield of the nanoparticles can be as high as4.5%in pure water. The upconversion nanoparticles were successfully used to label living cells with very high signal-to-noise ratio and excellent photostability. In particular, such blueemissive upconversion nanoparticles were successfully applied in lymph node imaging in vivo of living mouse with excellent signal-to-noise ratio (>25), upon low-power density excitation of CW laser (8.5mW cm-2).6) A general strategy for high-effective upconversion nanocapsules based on Triplet-Triplet AnnihilationWater-soluble nanocapsules exhibiting TTA-UCL emission were successfully prepared by loading sensitizer and annihilator into BSA-dextran stabilized oil droplets, which act as solvent for dissolving the sensitizer and annihilator. This strategy can maintain high translational mobility of the chromophores, avoid quenching by aggregation, and decrease the O2-induced TTA-UCL quenching, to produce high efficient UCL emission. The UCL quantum efficiency of UCNC-G and UCNC-Y can be as high as1.7%and4.8%, respectively, even under the atmospheric environment in water. In particular, these upconversion nanocapsules were successfully applied to lymph node imaging in vivo of living mouse without removing the skin, achieving excellent signal-to-noise ratios (>10), upon low-power density excitation by a CW laser (12.5mW cm-2).7) Enhanced photo-stability of NIR excitation TTA-UCL systemFor deep bioimaging, it is necessary of longer-wavelength emission for TTA-UCL. So far, TTA-UCL bioimaging is based on cell or the superficial parts of the body, such as lymph nodes. If we want to construt longer-wavelength emission (such as orange red emission) upconversion system based triplet-triplet annihilation for bioimaging, therer is one crucial problem needed to be resolved, photo-stability. In this section, we try to construct a kind of longer-wavelength emission, high photostibility and efficiency upconversion nanocapsule, in which the sensitizer and annihilator was dissolved in reducibility solvent (soybean oil). The reducibility solvent can decrease the effect of singlet oxygen to annihilator greatly and make the upconversion system keep good photostability.