稀土氟化物紫外上转换增强机制及其对光控药物释放性能的影响

Rare earth-doped ultraviolet upconversion luminescent materials have recently shown great promise in the biomedical field, benefitting from their specific optical property to convert low-energy light into high-energy photons. Low upconversion luminescence efficiency become a bottleneck of the development of upconversion materials. In this scientific research item, the ultraviolet upconversion enhancement mechanism of rare earth fluoride is particularly exploited to construct an intelligent drug delivery system which is controlled under 980 nm laser excitation. Different size rare earth upconversion luminescent nanomaterials will be prepared through a solvothermal route, which is based on the theory of effective separation of crystal nucleation and growth, and selective adsorption of surfactants in different crystal faces. By studying the relationship between the processes of energy transfer of rare earth ions and high-order energy level population, illuminates that high-order multi-photon processes depend on the composition, structure, size, defect, doped concentration, composition and structure of modified layer, and surface and interface structure of the rare earth fluoride materials, then reveals the ultraviolet upconversion luminescence enhancement mechanism of the prepared materials. In addition, mesoporous silica functionalized upconversion materials will be prepared by the Stöber method. Finally, the composite of upconversion materials and photoresponsive polymer will be synthesized by the Click Chemistry approach, and then high-order ultraviolet upconversion enhancement mechanism of materials will be discussed that how to influence photo-cleavage reaction of photoresponsive polymer and drug release. Our goal of this item is to obtain NIR light-controlled intelligent drug carries with low excitation power threshold and high conversion efficiency, and provide some useful experimental basis and technical support.

稀土掺杂紫外上转换发光材料可将低能光子转换为高能光子的特性使其在生物医学领域具有潜在应用价值。低的上转换效率成为其发展的瓶颈。本项目拟通过研究材料的紫外上转换发光增强机制，构建高效光控药物释放智能载药系统。基于晶体成核与生长的有效分离及表面活性剂对不同晶面的选择性吸附原理，通过溶剂热法制备不同纳米尺寸稀土上转换发光材料；研究稀土离子间能量传递过程对高阶能级布居的影响，阐明高阶多光子过程对材料的组成、结构、尺寸、缺陷、掺杂浓度、修饰层组成和结构、表界面结构的依赖关系，揭示制备材料紫外上转换发光增强的理论机制；采用Stöber法制备介孔硅修饰的上转换纳米复合材料，利用“点击化学”反应技术实现其与光响应聚合物的复合，探讨稀土上转换发光材料高阶紫外上转换增强机制对光响应聚合物中光切断反应及药物释放的影响规律，为构建低激发功率阈值、高转换效率、近红外光控智能药物载体提供实验依据和技术支持。

镧系离子由于具有独特的4f电子层结构及特有的功能特性使得其掺杂的稀土发光材料在光控药物释放、太阳能电池、光催化、光动力学治疗等领域显示出广阔的应用前景。在众多镧系离子掺杂的稀土发光材料中，NaREF4（RE = rare earth）基材料由于其低的声子能量、良好的化学稳定性等特性被认为是一种优异的基质材料。近年来，镧系离子掺杂的NaREF4基上转换发光材料因其独特的光学性质及其激发光源位于生物组织透过窗口等优点，成为光控药物释放载体的研究热点。然而，该类材料仍然存在发光效率较低、材料本身发光对组织穿透深度较浅等缺点，极大地限制了材料在生物医学领域的进一步应用。本项目基于晶体成核与生长的有效分离及表面活性剂对不同晶面的选择性吸附原理，通过溶剂热法及外延生长技术，制备了一系列不同种类的稀土上转换发光材料（NaLuF4:18%Yb,0.5%Tm,X%Fe, NaYF4:18%Yb,0.5%Tm, NaYF4:Yb3+,Er3+@ NaLuF4, NaGdF4:18%Yb,2%Er,X%Lu, NaYF4:18%Yb3+,2%Er3+@NaNdF4: 10%Yb3+）；研究了稀土离子间能量传递过程对高阶能级布居的影响，阐明高阶多光子过程对材料尺寸的依赖关系，揭示了纳米尺度下材料尺寸效应对紫外上转换发光增强的理论机制；在β-NaLuF4:18%Yb,0.5%Tm体系内引入Fe3+离子实现了上转换材料10倍高阶紫外上转换增强效应；通过深入研究Yb3+-Tm3+在不同尺寸下材料中的上转换发光性能，探讨尺寸效应对上转换发光特性的影响规律，实验数据表明尺寸为～30 nm材料具有最优的发光性能；通过自组装的方法，利用808 nm可激发的UCNPs、DASAs高分子和尼罗红（模型药物）成功制备了一种新型光控纳米药物载体。在低功率808 nm（0.2 W）激光照射下，纳米药物中UCNPs发出的绿光触发了高分子链上DASAs的异构化，破坏了纳米药物的亲疏水平衡，削弱了尼罗红与高分子疏水区域的相互作用，最终导致了尼罗红从纳米药物载体中逐步释放。总之，该项研究为构建低激发功率阈值、高转换效率、近红外光控智能药物载体提供实验依据和技术支持，进一步推动了此类纳米药物载体向临床医用迈进。