稀土掺杂钙钛矿量子点荧光探针：控制合成、光学性能和生物应用

Lanthanide-doped perovskite quantum dots (QDs), which bring together the advantage of the high photoluminescence (PL) quantum yield of perovskite QDs and the long PL lifetime of lanthanide (Ln3+), are promising as a new type of efficient luminescent probes for versatile biomedical applications. In this project, we aim to develop a novel type of luminescent bioprobes based on CsPbX3:Ln3+ perovskite QDs that are highly emissive in Ln3+ luminescence. The controlled synthesis, surface modification and bioconjugation of CsPbX3:Ln3+ QDs will be surveyed. The band-gap structures and luminescent mechanism of the QDs, as well as the local site-symmetry, electronic energy levels and excited-state dynamics of Ln3+ will be systematically investigated; the effect of quantum confinement on the electronic structures and luminescence of Ln3+ will be revealed. One or two types of efficient and practical luminophors will be selected to function as time-resolved luminescent bioprobes for sensitive and specific detection of squamous cell carcinoma antigen (SCC-Ag, an important tumor marker) in human saliva, thereby laying the foundation for the applications of these nanoprobes in early cancer diagnosis. The developed CsPbX3:Ln3+ QDs-based luminescent probes are expected to exhibit much more superior features in the PL intensity, photostability and sensitivity than traditional molecular probes such as organic dyes and Ln3+-chelates, and thus have great potentials in the fields of bioscience and clinical diagnosis.

稀土掺杂钙钛矿量子点有望结合量子点荧光量子产率高和稀土离子荧光寿命长的优点，成为新型高效的荧光探针应用于生物医学领域。本项目致力于研发具有高效带隙敏化稀土发光的CsPbX3:Ln3+钙钛矿量子点荧光探针，开展CsPbX3:Ln3+量子点的控制合成、表面修饰和生物偶联，研究钙钛矿量子点的带隙结构、发光机理以及稀土离子的局域位置对称性、电子能级和激发态动力学；揭示量子限域效应对稀土离子的电子结构和发光性能的影响；从中遴选出一、二种高效稳定的发光体系作为时间分辨荧光生物探针，实现对人体唾液中肿瘤标志物如鳞状细胞癌抗原（SCC-Ag）的高灵敏特异性体外检测，为该类荧光生物探针的肿瘤早期诊断奠定基础。预期本项目研制的CsPbX3:Ln3+钙钛矿量子点荧光探针在荧光强度、光化学稳定性和灵敏度等方面都表现出优于传统分子探针如荧光染料和稀土螯合物的良好性能，在生命科学和临床诊断等领域将发挥重要作用。

本项目主要围绕稀土掺杂无机纳米晶、稀土掺杂CsPbX3 (X = Cl, Br, I)钙钛矿量子点、稀土/钙钛矿量子点复合发光材料的控制合成、发光物理以及体外检测应用开展研究工作。按原定研究计划，项目组成功研制出一批单分散、发光效率高、稳定性好的CsPbX3:Ln3+ (Ln = Eu, Tb, Yb, Er等)以及稀土/钙钛矿量子点复合发光材料，并初步实现对人血清和唾液疾病标志物的高灵敏体外检测。在材料合成方面，项目组发展了HCl热注射、光诱导合成新方法，实现钙钛矿纳米晶及其复合结构的原位、实时限域合成。在光学性能方面，通过CsPbCl3量子点到Yb3+的量子剪裁过程获得110%的Yb3+的近红外发光量子产率；利用稀土敏化钙钛矿纳米晶，实现全光谱高效上转换/长余辉发光调控；揭示Mn2+在0D Cs4PbCl6与3D CsPbCl3钙钛矿纳米晶截然不同的激发态动力学。在生物应用方面，发展了稀土氟化物和硫化物等时间分辨和近红外二区纳米荧光探针，实现对癌胚抗原、人绒毛促性腺激素、黄嘌呤等疾病标志物的高灵敏、特异性体外检测。在项目执行期间，已在Nat. Commun., Angew. Chem. Int. Ed., Nano Today, Adv. Sci., Coord. Chem. Rev., Chem. Sci.等高档次SCI期刊发表论文28篇，其中影响因子大于14论文13篇、大于7论文24篇，1篇封底论文，1篇物理领域ESI高被引论文，所发表论文4年内被他引800多次。申请中国发明专利10项，其中6项已获授权。项目组较好地完成了预定的研究任务和研究目标。