The Polymer Society of Korea

Abstract

The field of optogenetics has enabled the fundamental understanding of neural circuits and disorders. However, these techniques require invasive surgical procedures to deliver light to target cells due to the low penetration depth of light into tissue. Therefore, ultrasound (US) was used as alternative trigger since US can deeply penetrate tissue with high spatiotemporal control. Our group develops molecular technologies based on polymer mechanochemistry to control the activity of drugs, proteins and nucleic acids by US. While initial efforts relied on low frequency (20 kHz) US that is destructive to cells, our current efforts are dedicated to two technology platforms that allow the activation of bioactive compounds by biocompatible US, i.e. imaging US and low intensity focussed US. The first technology relies on high molecular weight polynucleic acids that are produced by rolling circle amplification or transcription and that encode multiple binding sites for drugs, proteins and nucleic acids. Once these loaded nucleic acid carriers are subjected to US, non-covalent bond cleavage occurs by collapse of US-induced cavitation bubbles leading to activation of the cargoes. In this way, gene knock-down in vitro was achieved by liberating siRNA and immunostimulation was successfully realized in vivo by activating CpG oligonucleotides. Similarly, protein activity can be switched on by US, involving the mechanochemical activation of a protease that subsequently triggers split intein function for controlling the activity of a broad scope of proteins. A second platform technology for low-intensity US activation is mechanophore-incorporated microbubbles that also allow the spatiotemporally controlled release of bioactives.