In this paper, we first introduced a recently developed high-resolution, deep-tissue imaging technique, ultrasound-switchable fluorescence (USF). The imaging principles based on two types of USF contrast agents were reviewed. To improve USF imaging techniques further, excellent USF contrast agents were developed based on high-performance thermoresponsive polymers and environment-sensitive fluorophores. Herein, such contrast agents were synthesized and characterized with five key parameters: 1) peak excitation and emission wavelengths (λ_ex and λ_em); 2) the fluorescence intensity ratio between on- and off-states (I_On/I_Off); 3) the fluorescence lifetime ratio between on- and off-states (τ_On/τ_Off); 4) the temperature threshold to switch on fluorophores (T_th); and 5) the temperature transition bandwidth (T_BW). We mainly investigated fluorescence intensity and lifetime changes of four environment-sensitive dyes [7-(2-Aminoethylamino)-N,N-dimethyl-4-benzofurazansulfonamide (DBD-ED), St633, Sq660, and St700] as a function of temperature, while the dye was attached to poly(N-isopropylacrylamide) linear polymers or encapsulated in nanoparticles. Six fluorescence resonance energy transfer systems were invented in which both the donor (DBD-ED or ST425) and the acceptor (Sq660) were adopted. Our results indicate that three Förster resonance energy transfer systems, where both I_On/I_Off and τ_On/τ_Off are larger than 2.5, are promising for application in future surface tissue bioimaging by the USF technique.

中文翻译：

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基于热敏聚合物和纳米颗粒的超声可切换荧光成像对比剂的开发

在本文中，我们首先介绍了最近开发的高分辨率、深部组织成像技术，超声波可切换荧光 (USF)。回顾了基于两种类型的 USF 造影剂的成像原理。为了进一步改进 USF 成像技术，基于高性能热响应聚合物和环境敏感荧光团开发了出色的 USF 造影剂。在这里，这种造影剂被合成并用五个关键参数表征：1）峰值激发和发射波长（λ _ex和λ _em）；2) 开态和关态之间的荧光强度比（I _On /I _Off）；3) 开态和关态之间的荧光寿命比 (τ _On /τ _Off); 4) 开启荧光团的温度阈值 (T _th )；和 5) 温度转变带宽 (T _BW )。我们主要研究了四种环境敏感染料 [7-(2-氨基乙氨基)-N,N-二甲基-4-苯并呋喃磺酰胺 (DBD-ED)、St633、Sq660 和 St700] 作为温度的函数的荧光强度和寿命变化，而染料附着在聚（N-异丙基丙烯酰胺）线性聚合物上或封装在纳米颗粒中。发明了六种荧光共振能量转移系统，其中采用了供体（DBD-ED 或 ST425）和受体（Sq660）。我们的结果表明，三个 Förster 共振能量传递系统，其中 I _On /I _Off和 τ _On /τ_Off大于 2.5，有望应用于未来的 USF 技术表面组织生物成像。