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In Vivo Polymer Mechanochemistry with Polynucleotides.

Aman Ishaqat1,2, Johannes Hahmann1,2,3, Cheng Lin4,5

  • 1Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 2, 52074, Aachen, Germany.

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Summary

This study introduces a novel polynucleotide framework enabling medical ultrasound to trigger the release of therapeutic oligonucleotides. This breakthrough allows for force-controlled drug delivery and biological function activation in biomedical applications.

Keywords:
in‐vivopolymer mechanochemistryrolling circle amplificationsonogeneticssonopharmacology

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Area of Science:

  • Polymer Science
  • Biotechnology
  • Nanotechnology

Background:

  • Polymer mechanochemistry uses mechanical force to activate macromolecule functions, often with ultrasonication.
  • Current limitations in frequency and power intensity hinder biomedical applications of polymer mechanochemistry.
  • Medical ultrasound is a clinically established technology with potential for mechanochemical applications.

Purpose of the Study:

  • To develop a polynucleotide framework for therapeutic oligonucleotide delivery using medical ultrasound.
  • To enable force-induced binding and release of DNA and RNA cargo.
  • To explore applications in mechanochemistry-driven biological function activation.

Main Methods:

  • Design of a universal polynucleotide framework for cargo binding.
  • Utilizing biocompatible medical imaging ultrasound for force induction.
  • Demonstration of force-induced cargo release and biological activation in vitro and in vivo.
  • Characterization of high molar mass and colloidal assembly for mechanochemical mechanism.

Main Results:

  • Successful binding and release of therapeutic DNA and RNA oligonucleotides.
  • Demonstrated force-induced activation of biological function via ultrasound.
  • Established a novel platform for mechanochemical control in biological systems.
  • Validated in vitro and in vivo efficacy of the ultrasound-triggered system.

Conclusions:

  • A novel polynucleotide framework enables ultrasound-mediated polymer mechanochemistry for biomedical applications.
  • This platform facilitates force-controlled delivery and activation of oligonucleotide therapeutics.
  • Opens new avenues for exploring biological questions and developing therapeutics using mechanical force.