A method was developed to deliver therapeutic proteins inside the body using an acoustically sensitive carrier to encapsulate the proteins and ultrasound to image and guide the package to the exact location required. Ultrasound then breaks the capsule, allowing the protein to enter the cell. When the particle is exposed to ultrasound, it opens a hole in the cell membrane that lasts for a couple of microseconds. This temporary opening can be used to deliver antibodies, which are attractive therapeutic molecules in precision medicine that cannot otherwise get inside cells.
But getting the protein inside the nanoparticle carrier was not easy; the protein did not want to interact with the interior of the particle, which is made of a fluorous liquid similar to liquid Teflon. A fluorous chemical mask with a counterbalance of polarity and fluorine content was used to allow the protein to interact with the fluorous liquid medium while maintaining the protein’s folded state and bioactivity.
In future work, the team will explore the use of the ultrasound-programmable material as a platform for image-guided delivery of therapeutic proteins and gene editing tools. In related therapeutic applications, they are leveraging this technology to deliver antibodies that can alter abnormal signaling pathways in tumor cells to effectively turn off their malignant traits. In other work, they are delivering gene editing tools, like CRISPR constructs, to enable ultrasound-controlled genome engineering of cells in complex 3D tissue microenvironments.
These delivery applications can all be performed using ultrasound techniques already employed in hospitals, which will enable the rapid translation of this technology for precision healthcare.