Center for Research at Bio/Nano Interface, Department of Chemistry and Department of Physiology and Functional Genomics, UF Health Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida , Gainesville, Florida 32611-7200, United States.
Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Life Sciences, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University , Changsha 410082, China.
J Am Chem Soc. 2017 Apr 19;139(15):5289-5292. doi: 10.1021/jacs.7b00319. Epub 2017 Apr 7.
Exosomes are membrane-enclosed extracellular vesicles derived from cells, carrying biomolecules that include proteins and nucleic acids for intercellular communication. Owning to their advantages of size, structure, stability, and biocompatibility, exosomes have been used widely as natural nanocarriers for intracellular delivery of theranostic agents. Meanwhile, surface modifications needed to endow exosomes with additional functionalities remain challenging by their small size and the complexity of their membrane surfaces. Current methods have used genetic engineering and chemical conjugation, but these strategies require complex manipulations and have only limited applications. Herein, we present an aptamer-based DNA nanoassemblies on exosome surfaces. This in situ assembly method is based on molecular recognition between DNA aptamers and their exosome surface markers, as well as DNA hybridization chain reaction initiated by an aptamer-chimeric trigger. It further demonstrated selective assembly on target cell-derived exosomes, but not exosomes derived from nontarget cells. The present work shows that DNA nanostructures can successfully be assembled on a nanosized organelle. This approach is useful for exosome modification and functionalization, which is expected to have broad biomedical and bioanalytical applications.
外泌体是源自细胞的膜封闭细胞外囊泡，携带包括蛋白质和核酸在内的生物分子，用于细胞间通讯。由于其大小、结构、稳定性和生物相容性的优势，外泌体已被广泛用作治疗药物的细胞内递药的天然纳米载体。同时，通过其小尺寸和复杂的膜表面，赋予外泌体额外功能所需的表面修饰仍然具有挑战性。目前的方法已经使用了基因工程和化学偶联，但这些策略需要复杂的操作，并且应用有限。在此，我们提出了一种基于适配体的 DNA 纳米组装在细胞外囊泡表面。这种原位组装方法基于 DNA 适体与其细胞外囊泡表面标记物之间的分子识别，以及由适体嵌合触发物引发的 DNA 杂交链式反应。它进一步证明了对靶细胞来源的外泌体的选择性组装，但对非靶细胞来源的外泌体没有组装。本工作表明 DNA 纳米结构可以成功地组装在纳米级细胞器上。该方法对外泌体的修饰和功能化具有重要意义，有望在生物医学和生物分析领域得到广泛应用。
