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Logic-Gated Molecular Machines Encapsulate Environment-Responsive DNA Actuators for Tunable Cellular Lysosome
Xiuping Li1, Ruixue Chang1, Qiwei Wang1,2
1Department of Chemistry, University of Science and Technology of China, Hefei, China.
Angewandte Chemie (International Ed. in English)
|April 20, 2026
Summary
Larger DNA nanoassemblies cause greater cell damage by disrupting lysosomes. This study reveals how DNA nanostructure size controls cell death, guiding future nanotherapeutic design.
Area of Science:
- Biotechnology
- Nanomedicine
- Molecular Biology
Background:
- Intracellular DNA nanoassemblies can induce cell death.
- The relationship between DNA nanoassembly size and cellular interference is not well understood.
Purpose of the Study:
- To engineer a controllable DNA nanoassembly system for investigating scale-dependent lysosome interference.
- To elucidate the cell death pathways triggered by these nanoassemblies.
Main Methods:
- Development of a logic-gated, lysosome-targeted molecular machine with ATP-driven DNA actuators.
- Utilizing atomic force microscopy (AFM) and bio-transmission electron microscopy (bio-TEM) for visualization.
- Investigating cell death pathways via biochemical assays.
Main Results:
- Programmable DNA nanoassembly formation was achieved within the lysosome.
- Larger DNA assemblies demonstrated increased lysosomal membrane permeabilization and cytotoxicity.
- Cathepsin-mediated, caspase-independent cell death was identified as the primary pathway.
Conclusions:
- DNA nanoassembly size significantly influences lysosome interference and cell death.
- This programmable system offers insights for designing DNA nanostructures for cellular regulation.
- The findings establish a new framework for DNA-based nanotherapeutics.
