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Size-selected DNA hydrogels-based sensor with efficient intracellular delivery for imaging mRNA
Shufen Yao1, Shufang Wang1, Yinglin Meng1
1Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, China.
Talanta
|October 8, 2025
Summary
Researchers optimized DNA hydrogels for cell imaging by controlling their size. DNA hydrogels12, at 8.2 nm, showed the best cellular uptake and detection, offering insights for DNA hydrogel biosensors.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Molecular Biology
Background:
- Efficient intracellular delivery of DNA-based single-component hydrogels (DNA hydrogels) is crucial for cell imaging applications.
- The size of nanomaterials significantly influences their intracellular delivery efficiency.
- Developing size-controlled DNA hydrogels is essential for optimizing their biological applications.
Purpose of the Study:
- To investigate the effect of size on the intracellular delivery and performance of DNA hydrogels.
- To identify an optimal size for DNA hydrogels for enhanced cellular uptake and biosensing capabilities.
- To design and synthesize size-tunable DNA hydrogels for specific biological targets.
Main Methods:
- Fabrication of three distinct four-armed DNA structural units (unit15, unit12, unit9) with estimated diameters of 10.2 nm, 8.2 nm, and 6.1 nm.
- Assembly of these units into size-controlled DNA hydrogels (DNA hydrogels15, DNA hydrogels12, DNA hydrogels9) using DNA linkers.
- Evaluation of hydrogel response to target c-myc mRNA, including response time and limit of detection, and assessment of cellular uptake via fluorescence imaging.
Main Results:
- DNA hydrogels12 (8.2 nm) exhibited a faster response time (30 min) and a lower limit of detection (67.6 pM) compared to DNA hydrogels15 (10.2 nm).
- Fluorescence imaging revealed that DNA hydrogels12 achieved approximately two times higher cellular internalization than DNA hydrogels15.
- DNA hydrogels9 (6.1 nm) showed the fastest response (20 min) but a higher limit of detection (90.0 pM).
Conclusions:
- DNA hydrogels12 represent an optimal size for efficient intracellular delivery and effective biosensing applications.
- Size-dependent cellular uptake and performance highlight the importance of nanomaterial dimension in biological contexts.
- These findings provide valuable insights for the rational design of DNA hydrogel-based biosensors for improved cellular imaging and diagnostics.

