State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and KLMDASR of Tianjin, Nankai University, Tongyan Road, Haihe Education Park, Tianjin 300350, China.
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin 300071, China.
ACS Appl Mater Interfaces. 2020 Apr 8;12(14):16114-16124. doi: 10.1021/acsami.0c01715. Epub 2020 Mar 25.
Near-infrared (NIR) fluorescent probes can deeply penetrate through tissues with little damage. To facilitate image-guided theranostics, researchers usually apply a desired amount of photosensitizers to achieve effective photothermal responses. However, these probes could easily suffer from low photostability and aggregated-caused quenching effect in high concentrations. In this paper, the rational incorporation of an aggregated-induced emission (AIE) unit into the structure of heptamethine cyanine IR-780 is reported. Using tetraphenylethene (TPE) as an AIE core, we synthesize three TPE-modified IR-780 probes (IR-780 AIEgens) via different linkages. The IR-780 derivatives all show enhanced AIE features, in which the probe with an ether linkage (IR780-O-TPE) is superior in rapid cell uptake, high targeting capacity, and good photostability. Moreover, IR780-O-TPE exhibits the strongest cytotoxicity to HeLa cells (IC = 3.3 μM). The three IR-780 derivatives displayed a photothermal response in a concentration-dependent manner, in which IR-780 AIEgens are more cytotoxic than IR-780, with IC of 0.3 μM under 808 nm laser irradiation. In tumor-bearing mice, the optimal probe IR780-O-TPE also showed a more effective photothermal response than IR-780. By illustrating the relationship between aggregation state with photophysical properties, cell imaging, and cytotoxicity, this work is helpful in modulating NIR-based photosensitizers into AIE features for efficient image-guided theranostics.
近红外 (NIR) 荧光探针可以深入穿透组织，几乎没有损伤。为了便于图像引导的治疗，研究人员通常会施加一定量的光敏剂以实现有效的光热响应。然而，这些探针在高浓度下很容易受到低光稳定性和聚集引起的猝灭效应的影响。在本文中，报告了将聚集诱导发射（AIE）单元合理地引入到七甲川菁染料 IR-780 的结构中。我们以四苯乙烯（TPE）作为 AIE 核心，通过不同的键合方式合成了三种 TPE 修饰的 IR-780 探针（IR-780 AIEgens）。IR-780 衍生物均表现出增强的 AIE 特性，其中具有醚键的探针（IR780-O-TPE）具有快速的细胞摄取、高靶向能力和良好的光稳定性。此外，IR780-O-TPE 对 HeLa 细胞表现出最强的细胞毒性（IC = 3.3 μM）。三种 IR-780 衍生物均表现出浓度依赖性的光热响应，其中 IR-780 AIEgens 的细胞毒性强于 IR-780，在 808nm 激光照射下的 IC 为 0.3 μM。在荷瘤小鼠中，最佳探针 IR780-O-TPE 也表现出比 IR-780 更有效的光热响应。通过阐明聚集态与光物理性质、细胞成像和细胞毒性之间的关系，这项工作有助于将基于 NIR 的光敏剂调节为 AIE 特性，以实现高效的图像引导治疗。
