808nm激发的上转换纳米粒子的合成及生物应用

发布时间：2018-01-28 05:06

本文关键词： 808 nm激发上转换纳米粒子 Nd3+敏化上转换发光核壳结构 IR-806 光动力治疗生物成像　出处：《中国科学院研究生院(长春光学精密机械与物理研究所)》2015年博士论文　论文类型：学位论文

【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Na YF4: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。
[Abstract]:Rare earth ion doped upconversion luminescent nanoparticles can be low energy near infrared light into the near ultraviolet high energy to unique properties of visible light and near infrared light excitation, and in biological tissues (700~1100 nm), and the window of the near infrared excited excited luminescence (e.g. 980nm) with deep tissue penetration the depth and no other advantages. Since fluorescence upconversion nanoparticles are widely used as photodynamic therapy in biomedical, biological imaging, biological tracer and new functional nano drug carrier and so on, to show the important scientific research value and application prospect. Therefore, in recent years, the application of near infrared upconversion nanoparticles in the nano biomedical field has become a new research hotspot. Although widely used 980 nm near-infrared excitation upconversion nanoparticles has been widely applied in Biology The field of medicine. However, the water molecules in biological tissue absorption coefficient at the wavelength of 980 nm higher than an order of magnitude at the wavelength of 800 nm, the water molecules absorb 980nm light into heat, when using 980 nm excitation when the local tissue will produce a strong effect of overheating, causing thermal damage to local students tissue, but also reduces the near infrared tissue penetrating ability. These problems seriously affect the application of upconversion nanoparticles in biomedicine. The superheated effects of 980 nm light source excited, considering the water molecules in the 800 nm absorption is very weak, and the rare earth Nd3+ at 808 nm absorption very strong, and can be transferred to Yb3+ through non radiative resonance energy, so it can be sensitized in coordination with the Yb3+. We will move to the excitation wavelength of 808 nm, it can be a good thermal effect to avoid the uptake of water molecules produced by this theory. The main content of this paper is to synthesis and biological applications of upconversion nanoparticles based on the excitation of 808 nm. Mainly divided into the following aspects: synthesis and optimization of excitation of 1.808 nm Co doped upconversion nanoparticles were prepared by oleic acid salt path Na Co doped YF4:Nd/Yb/Ho upconversion nanoparticles through coordination and optimization of Nd3+, Yb3+ and Ho3+ concentration 808, to achieve efficient excitation of nm Co doped upconversion. And it is found that the doping concentration when changing the Yb3+ for the first time, doping concentration of Yb3+ has two maxima, and explain the mechanism of enhanced.2. preparation 808 nm excitation upconversion nanoparticles partition core-shell structure and extension of shell optimization by thermal injection of growth method for cladding the upconversion nanoparticles by sensitizer Nd3+ and luminescence center partition doped in the shell and core, thus inhibiting the quenching between Nd3+ and luminescent center ion Effect, and can inhibit the effect of surface defects. The shell of the role of nuclear Yb3+ in concentration can be increased to 20%~25%, while the shell in Nd3+ can be increased to 20%. after the luminous intensity of the core-shell optimal doping concentration of rare earth ion upconversion nanoparticles than Co doped upconversion luminescence enhanced 37.8 times.3. near infrared dyes enhance the excitation of 808 nm Nd3+ partition sensitized core-shell structure of upconversion luminescence due to overlapping IR-806 molecules in the vicinity of 800 nm and IR-806 absorption cross section and Nd3+ overlap integral JIR-806-Nd is much larger than the IR-806 and Yb3+ integral JIR-806-Yb, so IR-806 molecules will absorb the excitation light energy more efficiently through the fluorescence resonance energy transfer mode transfer to Nd3+ ions, can effectively sensitized core-shell structure excited by 808 nm upconversion. And core-shell structure nanoparticles coupling IR-806 upconversion dye After the child, the concentration of Nd3+ sensitized shell can be improved to 80%.IR-806 coordination Nd3+ sensitized core-shell structure upconversion luminescence intensity of IR-806 coordination than Yb3+ sensitized upconversion nanoparticles enhanced 76 times. BSA will use the dye sensitized core-shell structure coordination Nd3+ upconversion nanoparticles transferred to the aqueous phase, 808 nm stimulate cell imaging and photodynamic therapy 540 nm conversion cell fluorescence imaging.4.808 nm excitation thermal effect of upconversion nano photosensitizer partition core-shell structure 808 nm excited upconversion nanoparticles based on realized through covalent coupling method of photosensitizer rose red (RB) molecules on the surface of modified upconversion nanoparticles, and folic acid (FA) molecules covalently increased the conversion of nano photosensitizer targeting. In the aspect of building materials, we further optimized the Nd3+ shell thickness, achieve efficient upconversion luminescence and effective FR ET process, namely the relationship between light intensity and FRET on the conversion efficiency balance. Through the optimized shell thickness of 3 nm on the conversion of most singlet oxygen molecules to produce nanoparticles coupling photosensitizer, photodynamic treatment effect is the best, and the realization of biological target upconversion emission light of 540 nm markers. In addition to cell imaging the results of the study, confirmed that the 808 nm excitation photothermal effect produced far below the thermal effect of 980 nm excitation. No observed thermal damage.808 tissue nm excited upconversion nanoparticles is the recent development of a new type of upconversion luminescent materials, luminescent nano materials is expected to many challenges and promote the development of more powerful to other research fields such as biomedical and existing solutions to 808 nm excitation.

【学位授予单位】：中国科学院研究生院(长春光学精密机械与物理研究所)
【学位级别】：博士
【学位授予年份】：2015
【分类号】：TB383.1

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