Real-time monitoring ATP variation in human cancer organoids for a long term by DNA-based nanosensor

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.