光热转换与温度比率测量一体化的发光金纳米探针设计与应用研究

Accurate measurement of the transient heat generation during photothermal therapy is highly desirable and critical for medical diagnostics, cancer therapy and biological research. Due to its highly sensitive and non-invasive detection, fluorescence probe attracts increasing attention for the application in temperature sensing. However, it is still a challenge to prepare efficiently targeting fluorescent nanoprobes with good stability and sensitive temperature sensing to achieve accurately temperature-controlled photothermal therapy. In this project, with the assistance of self-assembly and cross-linked interaction, we will be devoted to the one-pot fabrication of multifunctional luminescent gold nanoassemblies with controllable morphology, photothermal conversion and ratiometric temperature measurement using thermosensitve amphiphilic block copolymers as the template. The luminescent gold nanoassemblies will consist of near-infrared absorbing organic photothermal agent and a nanothermometer, which will be prepared from a polarity-responsive hydrophobic dye and thermosensitve luminescent gold nanoparticles (AuNPs). The optical characteristics of luminescent AuNPs prepared using an in situ synthetic process will be comprehensively studied to find out the spectrum-tunable regularity, and the stability enhancement of gold nanoassemblies will be also studied using cross-linked interaction. Through controlling their size, morphology and surface targeting function, the effective strategy for the preparation of cancer cell-targeting nanoprobes will also be investigated. Furthermore, this project will systematically study the temperature-dependent emitting properties of the luminescent gold nanoassemblies, thus develop a novel temperature measurement system for photothermal therapy based on luminescent AuNPs, and apply it to the intracellular temperature imaging during photothermal therapy. This project would be able to offer a useful guidance for the preparation of multifunctional nanomaterials through self-assembly process, and provide a new path for non-invasive photothermal therapy with accurate temperature control.

光热疗法瞬态热的精准测量对医学诊疗和生物学研究具有重要意义。荧光探针法因其高灵敏度和非侵入性，在温度测量领域表现出巨大潜力。如何制备高稳定、温度灵敏、高效靶向的光热疗荧光纳米探针是实现精准温控光热疗的关键。本项目将利用自组装策略和交联作用，选取近红外吸收有机染料作为光热转换材料，将极性敏感有机染料与温敏发光金纳米粒子（AuNPs）组成温度比率探针，以温敏三嵌段共聚物为模板，一锅法制备结构可控、稳定、具有光热转换和温度比率测量功能的发光金纳米组装体。系统研究原位制备所需光谱性质的AuNPs和交联作用增强组装体稳定性的规律；调控粒径、形貌和表面靶向功能化，探讨癌细胞靶向性纳米探针有效制备策略。研究纳米组装体对温度的比率光学响应，构建出基于AuNPs的光热疗温度测量体系，并应用于细胞内光热疗温度成像分析，为自组装制备多功能纳米材料研究提供有益借鉴和指导，为非侵入式精准温控光热疗提供新的研究思路。

超小金纳米粒子(AuNPs)及其组装体由于其类分子光学特性、低毒、优异的光稳定性和易于制备等特点，是一类颇具应用潜力的新型发光纳米材料。然而，如何有效调控其发射与组装结构是实现温度精准测量、高肿瘤靶向等应用的关键。本项目以两亲性三嵌段共聚物Pluronic F127为模板，利用自组装策略和交联作用，一锅法制备出一系列结构可控、发射可调的发光金纳米组装体。通过调控疏水性巯基试剂（巯基齿数、烷基链长度）、还原剂强弱，系统性研究了发光AuNAs的发射波长、组装形貌的调控新方法；并探讨了AuNAs的组装形貌、表面化学与细胞摄取、肿瘤靶向的关系；通过杂化有机染料，构建了超灵敏、可逆温度比率测量体系；将AuNAs作为数据编码基元，探索了发光AuNPs在信息加密方面的新应用。本项目不仅为制备结构可控、高度稳定的功能化无机纳米组装体提供了新的研究思路，还为设计高灵敏度的化学传感、肿瘤高靶向成像应用提供了有益的指导。