Department of Biomedical Engineering, School of Life Science, Beijing Institute of Technology, Beijing, 100081, China.
Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China; Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
Anal Chim Acta. 2023 Sep 22;1275:341608. doi: 10.1016/j.aca.2023.341608. Epub 2023 Jul 11.
Cancer organoids have become promising tools for predicting drug responses on many different types of cancer. Detecting the adenosine triphosphate (ATP) has currently been considered as a decisive test to profile the growth status and drug responses of organoids. ATP profiling using commercial ATP detection kits, which involve cell lysis, can be performed at a single time spot, causing a clinical dilemma of selecting the optimal time spot to adopt diverse cancer types and patients. This study provides a feasible solution to this dilemma by developing a DNA-based ATP nanosensor to realize real-time ATP monitoring in organoids for a long term. The employment of DNA materials ensures high biocompatibility and low cytotoxicity, which are crucial for fragile organoids; The usage of tetrahedral DNA framework ensures cell permeability and intracellular ATP detection; The introduction of ATP-mediated molecular replacement ensures the high sensitivity and selectivity of ATP recognition. These features result in the first successful attempt on real-time monitoring ATP in organoids for up to 26 days and gaining growth status curves for the whole duration of a drug sensitivity test on human lung cancer organoids.
癌症类器官已成为预测多种癌症药物反应的有前途的工具。目前，检测三磷酸腺苷（ATP）被认为是一种决定性的测试，可以分析类器官的生长状态和药物反应。使用商业 ATP 检测试剂盒进行 ATP 分析，其中涉及细胞裂解，可以在单个时间点进行，这给选择最佳时间点以适应不同癌症类型和患者带来了临床困境。本研究通过开发基于 DNA 的 ATP 纳米传感器为这一困境提供了可行的解决方案，可实现类器官中 ATP 的长期实时监测。DNA 材料的使用确保了高生物相容性和低细胞毒性，这对脆弱的类器官至关重要；四面体 DNA 框架的使用确保了细胞通透性和细胞内 ATP 检测；ATP 介导的分子置换的引入确保了 ATP 识别的高灵敏度和选择性。这些特性使得首次成功尝试在类器官中实时监测 ATP 长达 26 天，并获得人类肺癌类器官药物敏感性测试整个过程中的生长状态曲线。
