Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan, 410082, China.
The Cancer Hospital of the University of, Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
Angew Chem Int Ed Engl. 2021 Jul 12;60(29):15816-15820. doi: 10.1002/anie.202103993. Epub 2021 Jun 11.
Tumor biomarker-based theranostics have achieved broad interest and success in recent years. However, single biomarker-based recognition can cause false-positive feedback, including the on-target off-tumor phenomenon, in the absence of tumor-specific antigen. Multibiomarker-based recognition molecules often elicit nonspecific and undesired internalization when they bind to "bystander" cells. We report a universal DNA tetrahedral scaffold (DTS) that anchors on the cell membrane to load multiple aptamers and therapeutics for precise and effective theranostics. This DNA logic-gated nanorobot (DLGN) not only facilitates precise discrimination among five cell lines, but also triggers synergistic killing of effector aptamer-tethered synergistic drugs (EASDs) to target cancer cells. Logic-gated recognition integrated into aptamer-functionalized molecular machines will prompt fast tumor profiling, in situ capture and isolation, and safe delivery of precise medicine.
近年来，基于肿瘤标志物的治疗诊断学已经引起了广泛的关注和成功。然而，在缺乏肿瘤特异性抗原的情况下，基于单一标志物的识别可能会导致假阳性反馈，包括靶标肿瘤外现象。基于多标志物的识别分子在与“旁观者”细胞结合时，往往会引起非特异性和不需要的内化。我们报告了一种通用的 DNA 四面体型支架 (DTS)，它锚定在细胞膜上以装载多个适体和治疗药物，用于精确和有效的治疗诊断学。这种 DNA 逻辑门控纳米机器人 (DLGN) 不仅可以精确地区分五种细胞系，还可以触发效应适体连接协同药物 (EASDs) 的协同杀伤，以靶向癌细胞。逻辑门控识别与适体功能化分子机器的集成将促使快速的肿瘤分析、原位捕获和分离以及精确药物的安全传递。
