Pukyong National University

“A Click of the Switch Selectively Cuts Target Molecular Bonds”

- Pukyong National University and RWTH Aachen University (Germany) Develop a DNA-Based Ultrasound Molecular Switch

- Selective bond cleavage achieved even under low-intensity ultrasound; expected applications in drug delivery and biosensors

Opening New Possibilities for DNA-Based Ultrasound Mechanophores

A research team led by Professor Kwak Min-Seok of the Department of Chemistry at Pukyong National University, in collaboration with the team of Professor Andreas Herrmann at RWTH Aachen University (Germany), has developed a DNA-based molecular switch (mechanophore) platform (DNA-MP-DNA) designed to selectively cleave specific molecular bonds when activated by the mechanical ‘force signal’ of ultrasound.

This technology has attracted attention for simultaneously addressing the low reaction efficiency and non-specific bond cleavage commonly observed in conventional polymer-based ultrasound mechanochemistry.

Previously, mechanophores were connected to flexible polymer chains to transmit ultrasonic forces. However, because of the flexible structure of polymers, the ultrasonic energy tended to disperse, making it difficult to deliver force precisely to the target bond. As a result, unintended bonds could break first or reaction times could become prolonged.

To overcome these limitations, the research team focused on the DNA double helix, which combines structural stability with partial flexibility. Compared with conventional polymers, DNA’s higher structural stability makes it more suitable for concentrating ultrasonic energy on the mechanophore site.

Development of a Precision Platform Achieving Selective Cleavage Within 15 Minutes

The research team designed a platform in which DNA strands of 100？1,000 base pairs (bp) are attached on both sides of the mechanophore. Experimental results showed that when the DNA structure reached a sufficient length (250 bp or longer), the cleavage rate at the mechanophore site reached about 99.9% within 15 minutes. DNA sequencing analysis confirmed that the DNA itself remained intact, while mass spectrometry precisely identified the cleavage location and pattern.

Professor Kwak Min-Seok explained, “If conventional polymer mechanophores are like a ‘hammer,’ DNA mechanophores are closer to a delicate ‘surgical scalpel.’ We believe this technology has strong potential to change the paradigm of mechanochemistry research.”

Potential as an Integrated Platform for Diverse Mechanophores

This platform also offers a significant advantage in that mechanophores with different structures can be easily exchanged, allowing their performance to be systematically compared and evaluated. The research team screened 32 candidate mechanophores using computational analysis (the CoGEF method) and experimentally validated several of them, enabling a systematic analysis of structural differences in reactivity.

Stable Operation Even Under Low-Intensity Ultrasound… Expanding Potential for Bio Applications

The research team also validated the platform under various ultrasound conditions, including laboratory equipment (20 kHz), ultrasonic cleaners (40 kHz), and cosmetic devices (1 MHz). Notably, in a low-intensity 1 MHz ultrasound experiment conducted under skin-like conditions, the system achieved over 80% selective bond cleavage without causing DNA damage, confirming its potential for practical use under medical ultrasound conditions.

The research team plans to expand this platform by integrating it with various biomaterials, such as DNA nanostructures and nanoparticle assemblies, enabling applications including ultrasound-triggered drug delivery systems, ultrasound-based biosensors, and smart therapeutic materials that respond to mechanical stimuli. The study is regarded as particularly significant because it combines DNA technology with polymer mechanochemistry, laying the groundwork for a new research field that enables precise control of molecular reactions using ultrasound.

This research was supported by the Nano and Materials Technology Development Program of the Ministry of Science and ICT and the National Research Foundation of Korea, as well as the Future Technology Research Lab and InnoCORE programs of the Ministry of Science and ICT, and the Regional Leading Research Center Program of the Ministry of Education. <Pukyong Today>