生物光学窗口有机染料的多光子上转换荧光、高分辨荧光成像及双光子光动力治疗研究

本项目基于全合成策略和巧妙的荧光团砌块设计，以荧光蛋白、近红外氟硼二吡咯、氧杂蒽及花菁为发光团，用可靠、高选择性的化学转变获得具有分子多样性和生物相容性的多光子荧光染料，建立生物光学窗口多光子荧光化合物库，发射波长覆盖近红外I-II区。通过灵巧化学修饰调控结构，控制分子衰变过程，拓展辐射衰变途径，堵塞或转化非辐射衰变过程，研究染料分子的多光子吸收、上转换荧光和能量转移机制。以双光子染料为光敏剂，系统开展荧光成像指导的肿瘤细胞双光子光动力治疗，揭示双光子光敏染料的光控能量传递及活性氧诱导肿瘤细胞凋亡机制，双光子光动力治疗在深层肿瘤治疗及抑菌等领域潜力巨大；以多光子染料为靶向荧光探针进行高分辨荧光成像，阐明探针与生物分子相互作用过程中非线性光学效应和荧光传感机制。本项目在生物体内多光子荧光成像、双光子光动力治疗、生物标记和荧光传感等领域具有非凡应用，研究十分迫切，科学意义尤其重大。

Multi-photon fluorescent dyes in the bio-optical window have wide range of applications in high-resolution three-dimensional imaging of biological systems, multi-photon fluorescent probe and two-photon-activated photodynamic therapy. Series of novel multi-photon fluorescent dyes are designed through total synthesis strategy and fluorophore building block. The research contents for the study are as follow: .(1)Multi-photon fluorescent compound library in the bio-optical window, containing fluorescent protein chromophore analogue, near-infrared BODIPY, near-infrared xanthene and cyanine;.(2) Multi-photon excited fluorescence properties of dyes in the bio-optical window and energy transfer; .(3) Two-photon-activated photodynamic therapy;.(4) Multi-photon fluorescent probes and high-resolution fluorescence imaging.. The multi-photon fluorescent dyes are designed using total synthesis strategy. These fluorescent dyes built from multi-photon fluorophores, including fluorescent protein chromophore analogue, near-infrared BODIPY, near-infrared xanthene and cyanine. The size and composition of dyes can be control accurately. The dyes produce a variety of colors and emission wavelength through structural control. Multi-photon absorption and multi-photon excited fluorescence properties of dyes are measured using a femtosecond Ti:sapphire laser. A detailed spectroscopic properties of these dyes, including absorption, fluorescence emission, fluorescence lifetime, fluorescence quantum yields, multiphoton excited fluorescence, multi-photon absorption cross-sections and aggregation-induced emission enhancement properties are studied and dye-loaded nanoparticles are prepared. The fluorescence emissive behavior and light-controlled energy transfer of multi-photon fluorescent dyes are researched. High-resolution fluorescence imaging and two-photon-activated photodynamic therapy are investigated.. The studies of multi-photon fluorescence processes and light-controlled of energy transfer give the information on structure-fluorescence relationships, which could provide clues to search for new multi-photon fluorescence dyes and applicate in biological labeling, fluorescent probe, high-resolution bio-imaging and two-photon-activated photodynamic therapy.