双模上转换纳米晶的研究及其在诊疗一体应用方面的探索

Upconversion nanoparticles have become promising luminescent biomarkers for applications ranging from molecular detection to cancer therapy, due to their unique capability to generate visible and even ultraviolet (UV) emissions under excitation in the near infrared (NIR) where biological tissues display minimal absorptions. Although biolabeling with upconversion nanoparticles has become the state-of-the-art with the potential to impact fundamental biomedical research and clinical practice, it is not without limitations and complications. For example, classical upconversion nanoparticles are not useful in theranostic applications because their excitation-independent optical properties can hardly offer temporally separated diagnostic and therapeutic processes. This proposal seeks to address the problems by developing a new class of dual-model upconversion nanoparticles that show distinct optical emissions in response to excitations of different wavelengths. Specifically, we aim to realize excitation wavelength switchable visible and UV emissions for the purposes of diagnosis and therapy, respectively. A significant amount of effort will also be devoted to boosting the upconversion efficiency in the high-energy UV spectral region. Once refined, we envisage that our study will open up new opportunities for therapeutic and diagnostic imaging applications that outperform existing upconversion techniques.

上转换纳米颗粒是一种可以将生物组织吸收微弱的近红外的激发光转换为可见甚至是紫外发光的纳米材料，因而特别适合作为荧光标记物用于分子检测和癌症治疗等领域。目前基于上转换已经发展了一类非常先进的生物标记技术，其对生物医学研究和临床诊断也产生了极大的积极影响。然而现有上转换颗粒的光学性质也制约了其进一步的发展。例如，传统的上转换纳米材料在治疗诊断学这一新兴应用中比较受限，因为其不依赖于激发光波长的发光性质很难提供实时分立的诊断和治疗过程。此计划书旨在设计一种新的双模上转换纳米材料以解决上述问题。此类上转换纳米材料能够在不同波长的激发条件下会产生波长动态变化的上转换发光。特别地，我们希望做到通过激发波长控制，实现可灵活转换的可见和紫光发光，分别用以实现诊断和治疗。同时我们会探索新的方法用以增强深紫外波段的发光效率，以提升现有上转换技术，开启其在治疗和诊断上的新应用。

本项目旨在突破传统的单模上转换纳米发光材料，通过改变激发波长获得在紫外和可见光区动态可调的发光波长，分别用于生物学的诊断和治疗。同时，我们也着力于提高上转换发光的强度，从而改善其在实际应用中的效力。围绕这些目标，本项目在稀土上转换发光材料的发光调控和生物应用方面取得了一系列创新性的研究成果。在上转换发光调控方面，通过精确合成稀土掺杂的核壳纳米结构，实现了808nm、980nm和1550nm激发的上转换发光过程，及其相互独立的光谱调控；解决了高浓度掺杂引起的浓度猝灭问题，提高了紫外上转换发光的强度。在此基础上，合成了一系列多功能上转换纳米复合材料，并以此为载体，通过表面修饰生物分子和担载药物分子如光敏铂药，利用上转换纳米材料的独特性质，实现高灵敏的生物检测以及近红外光控制的药物释放以及肿瘤的联合治疗。项目执行期间共计在Nat. Commun., Angew. Chem., Adv. Funct. Mater., Acc. Chem. Res., Small等相关领域的核心杂志上发表SCI论文22篇，项目负责人入选2018年全球“高被引科学家”榜单；入选2017年英国皇家化学会1%顶尖高被引作者。