Parkes Ellen, Al Samad Assala, Mazzotti Giacomo, Newell Charlie, Ng Brian, Radford Amy, Booth Michael J
Department of Chemistry, University of Oxford, Oxford, UK.
Department of Chemistry, University College London, London, UK.
Nat Chem. 2025 Sep 2. doi: 10.1038/s41557-025-01909-6.
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.
合成细胞的灵活且模块化设计，包括能够模仿活细胞结构和功能的脂质囊泡，便于其作为药物递送装置的应用。利用组织穿透性刺激来控制合成细胞内生物分子的合成的能力开启了额外的功能层面，这有可能提高生物学效力并避免预装载囊泡中的药物泄漏。为此，我们设计了球形核酸，其由装饰在磁性纳米颗粒核心上的DNA启动子序列组成。这些球形核酸使我们能够利用磁热疗（一种临床批准的抗癌疗法）散发的热量来调节无细胞蛋白质合成并按需释放货物。此外，这种生物合成的磁调节是使用临床可耐受的磁场强度和频率实现的。然后，我们部署了一种当前激活方法无法穿透的不透明阻挡材料，以突出该技术利用体内深处的组织穿透性磁场靶向和控制生物分子原位合成的潜力。
