School of Chemistry & Environment, South China Normal University , Guangzhou 510006, China.
Departments of Physiology and Developmental Biology, University of Texas , Southwestern Medical Center, Dallas, Texas 75390-9133, United States.
J Med Chem. 2016 Jan 14;59(1):410-8. doi: 10.1021/acs.jmedchem.5b01622. Epub 2015 Dec 31.
We report biological evaluation of a novel nanoparticle delivery system based on 1,1,2-triphenyl-2-(p-hydroxyphenyl)-ethene (TPE-OH, compound 1), which has tunable aggregation-induced emission (AIE) characteristics. Compound 1 exhibited no emission in DMSO. In aqueous media, compound 1 aggregated, and luminescence was observed. The novel membrane-cytoplasm-nucleus sequential delivery strategy could induce apoptosis in four different kinds of cancer cells (including three adherent cell lines and one suspension cell line). The nanoparticles remained in the cytoplasm with intense blue emissions, whereas doxorubicin was observed in the nucleus with striking red luminescence. The nanoassembly was internalized in cells through an energy-dependent process. Three sorts of chemical inhibitors were used to clarify the endocytosis mechanism based on the AIE type prodrug. Furthermore, we have developed the first AIE theranostic system where drug targeting and release have been applied in an animal model.
我们报告了一种基于 1,1,2-三苯基-2-(对羟基苯基)乙烯（TPE-OH，化合物 1）的新型纳米颗粒递药系统的生物学评价，该系统具有可调节的聚集诱导发射（AIE）特性。化合物 1 在 DMSO 中没有发射。在水介质中，化合物 1 聚集，观察到发光。新型的膜-细胞质-核顺序递药策略可以诱导四种不同类型的癌细胞（包括三种贴壁细胞系和一种悬浮细胞系）凋亡。纳米颗粒在细胞质中保持强烈的蓝色发射，而阿霉素在细胞核中观察到明显的红色发光。纳米组装通过能量依赖的过程被细胞内化。三种化学抑制剂被用于基于 AIE 型前药阐明内吞作用机制。此外，我们已经开发了第一个 AIE 治疗系统，其中药物靶向和释放已应用于动物模型。
