Real-time monitoring ATP variation in human cancer organoids for a long term by DNA-based nanosensor
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Updated: Jul 20, 2025

Multiparametric Tumor Organoid Drug Screening Using Widefield Live-Cell Imaging for Bulk and Single-Organoid Analysis
Published on: December 23, 2022
Kexin Zhang1, Yadong Wang2, Jianchao Xue2
1Department of Biomedical Engineering, School of Life Science, Beijing Institute of Technology, Beijing, 100081, China.
Abstract:
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.
Insights
Researchers developed a novel DNA-based nanosensor for real-time monitoring of adenosine triphosphate (ATP) in cancer organoids. This breakthrough enables long-term growth tracking and drug response assessment, overcoming limitations of current methods.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Nanotechnology
Background:
- Cancer organoids are valuable for predicting drug responses.
- Adenosine triphosphate (ATP) detection is crucial for assessing organoid growth and drug efficacy.
- Current ATP detection methods are limited to single time points, hindering comprehensive analysis.
Purpose of the Study:
- To develop a novel DNA-based ATP nanosensor for real-time, long-term monitoring of ATP levels in cancer organoids.
- To overcome the limitations of current single-time-point ATP detection methods.
- To enable continuous monitoring of organoid growth status and drug responses.
Main Methods:
- Development of a DNA-based nanosensor utilizing a tetrahedral DNA framework for enhanced cell permeability and intracellular detection.
- Incorporation of ATP-mediated molecular replacement for sensitive and selective ATP recognition.
- Real-time ATP monitoring in human lung cancer organoids for up to 26 days.
Main Results:
- The developed DNA-based ATP nanosensor demonstrated high biocompatibility and low cytotoxicity.
- The nanosensor achieved real-time intracellular ATP detection within organoids.
- Successfully generated growth status curves for organoids over a 26-day period during drug sensitivity testing.
Conclusions:
- The DNA-based ATP nanosensor offers a feasible solution for real-time, long-term ATP monitoring in cancer organoids.
- This technology overcomes the clinical dilemma of selecting optimal time points for ATP detection.
- Enables comprehensive assessment of organoid growth and drug responses, advancing personalized cancer therapy.
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