Magnetic activation of spherical nucleic acids enables the remote control of synthetic cells

Abstract The flexible and modular design of synthetic cells, comprising lipid vesicles capable of imitating the structure and function of living cells, facilitates their application as drug delivery devices. The ability to control the synthesis of biomolecules within synthetic cells using a tissue-penetrating stimulus opens up additional levels of functionality that has the potential to improve biological potency and circumvent drug leakage from preloaded vesicles. To this end, we have designed spherical nucleic acids comprising DNA promoter sequences decorating magnetic nanoparticle cores. These spherical nucleic acids allowed us to harness the heat dissipated from magnetic hyperthermia (a clinically approved anticancer therapy) to regulate cell-free protein synthesis and release cargo on demand. Furthermore, this magnetic regulation of biosynthesis was achieved using clinically tolerable magnetic field strengths and frequencies. We then deployed an opaque blocking material that is impenetrable by current activation methods to highlight the potential of this technology for targeting and controlling the in situ synthesis of biomolecules using tissue-penetrating magnetic fields deep within the body.