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题名	808 nm激发的上转换纳米粒子的合成及生物应用
作者	王丹
学位类别	博士
答辩日期	2015-05
授予单位	中国科学院大学
导师	孔祥贵
关键词	808 nm激发 IR-806 上转换纳米粒子 光动力治疗 Nd3+敏化 生物成像 上转换发光 核壳结构
其他题名	Synthesis and Bio-applications of Upconversion Nano-particles under 808 nm Excitation
学位专业	凝聚态物理
中文摘要	稀土离子掺杂的上转换发光纳米粒子能将低能量的近红外光转化为高能量的近紫外到可见光的独特性质，而且激发的近红外光又位于生物组织窗口(700～1100 nm)，因而对其激发的近红外激发光(例如980nm)具有较深的组织穿透深度和无自荧光等优点。上转换发光纳米粒子广泛应用于生物医学诸如光动力学治疗、生物成像、生物示踪和新型多功能化的药物纳米载体等方面，展现了重要的科学研究价值和应用前景。因此，近些年来，针对近红外上转换发光纳米粒子及其在纳米生物医学领域的应用成为研究的新热点。尽管普遍采用980 nm近红外光激发的上转换纳米粒子越来越广泛地用于生物医学等领域。然而，生物组织中的水分子在980 nm波长处的吸收系数比在800 nm波长处要高一个数量级，水分子吸收980nm光转化成热，当用980 nm激发时局部组织会产生很强的过热效应，从而导致局域生物组织的热损伤，同时也降低了近红外光的组织穿透能力。这些问题严重地影响了上转换发光纳米粒子在生物医学中的应用。针对980 nm光源激发产生的过热效应问题，考虑到水分子在800 nm处的吸收很弱，而且稀土Nd3+在808 nm处有很强的吸收，并可以通过无辐射共振能量传递给Yb3+，因此可以与Yb3+协同敏化。我们将激发光的波长移动到808 nm，恰好可以很好的避免水分子的吸收而产生的热效应。本论文研究的主要内容是基于808 nm激发的上转换纳米粒子的合成及生物应用。主要分为以下几个方面： 1. 808 nm激发共掺杂的上转换纳米粒子的合成及优化 采用油酸盐路径法制备共掺杂NaYF4：Nd/Yb/Ho上转换纳米粒子，通过协调优化Nd3+，Yb3+和Ho3+掺杂浓度，实现808 nm激发的高效的共掺杂上转换发光。并首次发现当改变Yb3+的掺杂浓度，Yb3+的掺杂浓度有两个极大值，并解释相关机理。 2. 增强808 nm激发上转换纳米粒子分区核壳结构的制备及优化 采用高温热注入的外延壳生长方法对上转换纳米粒进行包壳，通过将敏化剂Nd3+和发光中心分区掺杂在壳和核中，从而抑制了Nd3+和发光中心离子之间的猝灭效应，并可以有效的抑制表面缺陷效应。通过包壳的作用，核中Yb3+浓度可以提高到20%～25%，而壳中的Nd3+可以提高到20%。经过优化稀土离子掺杂浓度的核壳上转换纳米粒子的发光强度比共掺杂上转换发光增强37.8倍。 3. 近红外有机染料增强808 nm激发Nd3+敏化分区核壳结构的上转换发光 由于IR-806分子在800 nm附近的吸收截面大及其IR-806与Nd3+的交叠积分JIR-806-Nd要远大于IR-806和Yb3+的交叠积分JIR-806-Yb ，因此IR-806分子将吸收的激发光能量更有效地通过荧光共振能量传递方式传递给Nd3+离子，能够更有效的敏化808 nm激发的核壳结构的上转换发光。并且核壳结构的上转换纳米粒子偶联染料IR-806分子后,Nd3+敏化壳层的浓度可以提高到80%。IR-806协调Nd3+敏化核壳结构的上转换发光比IR-806协调Yb3+敏化上转换纳米粒子的发光强度增强76倍。利用BSA将这种染料协调Nd3+敏化核壳结构的上转换纳米粒子转移到水相，实现了808 nm激发540 nm上转换细胞荧光成像。 4. 808 nm激发低热效应的上转换纳米光敏剂的细胞成像及光动力治疗 基于808 nm激发的分区核壳结构的上转换纳米粒子，通过共价偶联的方式将光敏剂玫瑰红(RB)分子修饰到上转换纳米粒子的表面，同时共价叶酸(FA)分子增加上转换纳米光敏剂的靶向性。在材料构建方面，我们进一步优化Nd3+壳层的厚度，实现高效的上转换发光和有效的FRET过程，即平衡上转换的发光强度和FRET效率之间的关系。经过优化后的壳层厚度为3 nm的上转换纳米粒子偶联光敏剂分子产生的单线态氧最多，光动力的治疗效果最佳，并且实现上转换的发射光540 nm的生物靶向标记细胞成像。另外，研究结果证实，808 nm激发产生的光热效应远低于980 nm激发产生的热效应。没有观察到生物组织的光热损伤。 808 nm激发的上转换发光纳米粒子是近来发展的一类新型上转换发光材料，808 nm激发的上转换发光纳米材料有望更强有力促进和带动诸如生物医学等其它研究领域的发展及其存在的许多挑战性难题的解决。
英文摘要	Lanthanide doped upconversion nannoparticals (UCNPs) have received many at-tentions over the past few years. UCNPs havemany excellent properties including large anti-Stokes shift, narrow-band emission, no photobleaching and no photoblink-ing, low toxicity and so on. In addition, near-infrared light was employed as excitation light which brings about high penetration depth, and low biological autofluorescence background. Based on these superior physicochemical features, UCNPs have been successfullyused in biolabeling, bioimaging and photodynamic therapy, photovoltaics. However, 980 nm light was used to trigger Yb3+-sensitized upconversion nanoparticals, which also absorbed by the water component in biological tissues thus limits penetration depth and caused severe overheating effects. To avoid this overheating effect, shifting the excitation wavelength to 808 nm is an elegant way because water has little absorption around this range. Moreover, Nd3+ ions can be used as new sensitizers due to Nd3+ions feature a sharp absorption band centered at 808 nm. The main contents of this dissertation are about synthesis and bio-applications of UCNPs under 808nm excitation, which include five parts: (1) we synthesized NaYF4:Nd/Yb/Ho codoped upconversion nanoparticals and studied their upconversion luminescence (UCL) under 808 nm excitation. Optimal doped concentration of different ions was explored. High upconversion luminescence was achieved by modulating Nd3+, Yb3+ and Ho3+ concentrations. Especially, we found that two peaks appeared when plotting luminescence intensity against Yb3+ concentration, and explained this phenomena. (2) We synthesized Nd3+ ions sensitized core-shell nanostructure and optimized their UCL intensity under 808 nm excitation. To avoid quenching effect, we spatially separated Nd3+ ions in the shell and Ho3+ ions in the core. Compared with codoped structure, the concentration of Nd3+ was elevated to 20%, and Yb3+ was elevated to 20%～25%. In particular, the UCL of core-shell structure remarkably increased 37.8 times. (3) We constructed near-infrared organic dye (IR-806) mediate Nd3+-sensitized core-shell upconversion nanoparticals to enhance UCL under 808 nm excitation. Up-conversion emission of NaYF4:Yb/Er@NaYF4:Yb@NaYF4:Nd core-shell-shell nano-crystals increased largely when bonded with near-infrared dye (IR-806), We proved that energy transfer efficiency from IR-806 to Nd3+ more efficient than IR-806 to Yb3+ due tolarge spectral overlap between emission of IR-806 and absorption of Nd3+. We also transferred these IR-806 mediate Nd3+-sensitized core shell UCNPs to water to perform bioimaging. (4) We performed photodynamic therapy (PDT) experiments under 808 nm exci-tation. In vivo biological application of upconversion nanoparticles (UCNPs) prefers excitation of 700-850 nm, instead of 980 nm, due to the less absorption of 808 nm for water. Recently approach in constructing robust Nd3+doped UCNPs subject to 808 nm excitation relies on a thick Nd3+ sensitized shell. However, for the very important and popular Förster resonance energy transfer (FRET)-based applications, such as photo-dynamic therapy (PDT) or switchable biosensor, this structure has its restriction re-sulting in a poor energy transfer. We have in this work designed the NaYF4:Yb/Ho@NaYF4:Nd@NaYF4 core-shell-shell nanostructure. It is proved that this optimal structure balances the robustness of the upconversion emission and the FRET efficiency for FRET-based bio-application. A proof of the concept was demon-strated for photodynamic therapy and simultaneous fluorescence imaging of Hela cell triggered by 808 nm light, where low heating and high PDT efficiency were reached. It was well known that UCNPs excited by 808nm is a new material of UCL de-veloped in the last two years. This new material will take great effort for solving the challenging problems in the field of biomedical research.
公开日期	2015-12-24
内容类型	学位论文
源URL	[http://ir.ciomp.ac.cn/handle/181722/48902]
专题	长春光学精密机械与物理研究所_中科院长春光机所知识产出
推荐引用方式 GB/T 7714	王丹. 808 nm激发的上转换纳米粒子的合成及生物应用[D]. 中国科学院大学. 2015.

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