745nm光激发单谱带发射稀土上转换纳米晶的制备及在深组织生物成像中的应用

Lanthanide-doped upconversion nanoparticles (UCNPs) has an important application value in biological imaging. Currently, UCNPs used for deep-tissue imaging still has some shortages: (1) Continuous laser irradiation at 980 nm would lead to a risk of local temperature rise, and substantial overheating may even induce tissue damage and decrease the light penetration depth into biological tissues; (2) Multi-band emission of UCNPs, especially the emission peaks outside the biological window, cause interference to biological imaging signal, resulting in the decrease of the resolution and sensitivity; (3) The luminescent intensity of UCNPs should be further enhanced. To solve the above issues, high efficient Nd3+-sensitized single-band emission UCNPs, of which the excitation (745 nm) and emission wavelength (660 nm or 800 nm) are located at biological window, has been designed via the selection of rare earth/transition metal ions and the construction of core-shell-shell nanoarchitecture. This project will involve the following parts: (1) The design, synthesis and performance optimization of 745 nm NIR light excited core-shell-shell UCNPs; (2) Mechanistic investigation of Mn2+ dopant-induced single-band upconversion emission in Nd3+-sensitized nanoparticles; (3). The application of the as-designed UCNPs in deep-tissue bioimaging. The present project can further enrich the research content of UCNPs and provide reference for the design and synthesis of high efficient UCNPs for deep-tissue imaging.

上转换纳米材料(UCNPs)在生物成像领域具有重要的应用价值。目前，生物成像用UCNPs仍存在一些不足：（1）激发光照射产生局部过热风险，易引起生物组织损伤和降低光穿透深度；（2）稀土离子的多峰发射，特别是生物窗口外的发射峰对成像信号造成干扰，降低了成像分辨率和灵敏度；（3）上转换发光强度有待进一步提高。针对上述问题，本项目拟通过稀土/过渡金属离子的选择和核-壳-壳纳米结构的设计来构建激发（745 nm）和发射峰（660 nm或800 nm）均位于生物窗口区的高效Nd3+敏化单带上转换发光体系。主要研究内容包括：（1）高效745 nm光激发核-壳-壳上转换体系的设计、制备与性能优化；（2）Mn2+掺杂诱导Nd3+敏化单带上转换发光机理研究；（3）新型UCNPs在深组织生物成像中的应用探索。本项目的实施进一步丰富上转换纳米材料的研究内容，为深组织生物成像用UCNPs的研发奠定理论和实验基础。

上转换纳米材料因具有窄带发射、长荧光寿命、优异的光稳定性和低毒性等优点，尤其是用于激发的近红外光具有较大的组织穿透深度和不会引起自发荧光的独特性质，在生物成像领域展现了巨大的应用前景。但仍然面临激发光引起热效应、稀土离子多峰发射及上转换发光强度有待提高等问题。为了解决这些问题，本项目以Nd3+、Yb3+和Er3+作为敏化离子、能量传递“桥梁”和发光离子，立方相NaYF4@CaF2@NaNdF4核壳壳结构作为掺杂基质，采用共沉淀法制备NaYF4：Yb/Er@CaF2:Yb@NaNdF4:Yb纳米颗粒。为了实现高效745nm激发下Er3+上转换发光现象，我们首先通过优化核、壳、壳层中Yb3+的掺杂浓度，结果显示最佳掺杂浓度分别为30 mol%，20 mol%和10 mol%。接下来，在α-NaYF4内核掺杂Mn2+实现Nd3+敏化Er3+单谱带红色上转换发光。研究结果表明Mn2+离子的掺杂浓度达到35 mol%，上转换纳米颗粒在745nm激光激发下获得单谱带红色上转换发光峰。最后，优化的上转换纳米材料进行亲水化处理，并且进行了生物相关验证性实验。相比于980nm激发下，745nm激发的上转换纳米颗粒具有更深的生物组织穿透深度及较低的热效应，更适用于深组织生物成像。综上所述，我们已经对本基金提出的问题进行了系统的研究，并取得了有意义的结果和成果，顺利地完成了本自然科学基金项目。