染料级联敏化蛋白质尺寸稀土氟化物核壳纳米晶的构筑与性质研究

The key for proverbial biomedical applications of rare earth upconverting materials lies in the ability to prepare protein-sized nanomaterials, which can enable a rapid renal clearance from the body to prevent any potential biological toxicity. However, it is challenging to prepare such fluoride materials, which also exhibit exceptionally weak upconversion luminescence. Here, we propose to develop a solution-based nanochemical approach to grow protein-sized, hexagonal crystallographic phase, gadolinium-based fluoride core/shell nanocrystals, having a single atomic layer deposition precision for an epitaxial growth of the shell layer. The epitaxial core/shell structure is able to suppress the strong surface-related quenching for the ultrasmall-sized core nanocrystals, thus remarkably boosting the upconversion luminescence efficiency. Furthermore, we will develop a hybrid organic-inorganic nanosystem consisting of an epitaxial core/active shell upconverting nanocrystal with the organic NIR dye molecules anchored on to the nanocrystal surface. The NIR dyes are designated to broadly and strongly harvest NIR light, with subsequent nonradiative energy transfer to the lanthanide sensitizers of Nd3+ ions in the shell, and then to the lanthanide ions positioned within the inorganic core. This hybrid system retains the merit of the high efficiency of the core/shell structure, while circumventing the narrow and weak 4f absorption of rare earth ions, thus enabling to produce an unprecedented high upconversion luminescence efficiency. The results to be achieved will constitute a solid step forward to advance rare earth upconverting materials towards marketing.

稀土上转换材料在生物医学领域实用化的关键在于制备肾脏可代谢的超小尺寸纳米晶，消除其生物毒性。然而，满足此目的的蛋白质尺寸大小的纳米晶不但合成困难而且上转换发光强度极弱，严重阻碍其应用前景。针对于此，本项目拟通过单原子层精度的液相体系外延生长法制备具有 蛋白质尺寸、六角晶相结构、钆基核壳结构稀土氟化物纳米晶；不但严格具有肾脏可排出的小尺寸效应，而且能充分抑制内核纳米晶表面无辐射跃迁过程，从而极大增加上转换发光效率。特别是拟进一步利用宽带强吸收的红外有机染料分子对核壳结构纳米晶进行能量级联敏化，突破稀土离子4f-4f跃迁吸收弱和窄的本征限制，实现蛋白质尺寸核壳纳米晶上转换效率百倍量级的增加，从而成功应用于高清晰上转换和核磁双模态小鼠成像。高上转换发光效率蛋白质尺寸稀土氟化物纳米晶复合结构材料的实现，为推进稀土荧光材料实用化进程奠定了坚实的基础。

稀土基上转换材料在生物医学领域实用化的关键在于制备可代谢的蛋白质尺寸纳米晶，从而消除其潜在生物毒性；然而，此类纳米晶不但合成困难且上转换发光强度极弱。针对于此，本项目发展了一种液相高温共沉淀制备方法实现蛋白质尺寸单核和核壳纳米晶精准制备，同时采用宽带强吸收的红外有机染料分子对纳米晶进行能量级联敏化，突破稀土离子4f-4f跃迁吸收弱和窄的本征限制，实现上转换发光强度26172倍增强（相比单核纳米晶），并成功应用于上转换和核磁双模态小鼠成像和体内排除。具体地，第一年我们采用高温共沉淀方法成功制备尺寸均一、六角相NaGdF4:Yb,Er小尺寸纳米晶(最小3-4 nm)，并单原子精度外延生长NaGdF4 惰性层（如1-2 nm），增强单核上转换1000倍；寿命分析研究证明核壳结构能有效抑制表面淬灭效应。第二年，进一步制备出形貌均一、尺寸<6 nm的NaGdF4:30%Yb3+/2%Er3+@NaGdF4:Yb3+/Nd3+激活核/激活壳纳米晶，将近红外有机染料IR-783配位到纳米晶表面构筑有机-无机纳米晶复合体系 实现 “天线效应”敏化。研究结果表明有机染料-纳米晶复合体系出现新的宽和强吸收峰（750-840 nm, IR-783染料吸收），增强上转换发光40-60倍。第三年我们基于项目前期发展的蛋白质尺寸纳米晶的合成工艺，进一步制备NaYF4:50%Gd3+/20%Yb3+/2%Er3+@NaGdF4:X%Yb3+（X=0，20，40，70，100）核壳纳米晶，并探究IR806等染料（发射与稀土离子具有更大的光谱重叠）单线态和三线态在空气或无水、无氧条件下级联敏化作用。研究结果表明最优敏化条件下，染料敏化增强单核纳米晶吸收430倍和核壳结构纳米晶4798倍；与单核纳米晶相比，最优染料敏化发光增强26172倍。染料敏化使得体系激发波长从980 nm频移到800 nm附近，克服水分子对980 nm光强吸收引起的生物热效应的问题。第四年采用磷脂双层分子包覆成功制备水相稳定的染料敏化核壳纳米晶（实现水相体系发光400倍增强），成功实现小鼠上转换和核磁共振双模态动态成像，并能通过肝脏和肾脏代谢途径排除体外 （5天排除70%以上）。综上所述，我们成功完成自然科学基金计划的所有内容。