Domain-Targeted Membrane Partitioning of Specific Proteins with DNA Nanodevices.

The cell membrane exhibits a remarkable complexity of lipids and proteins that dynamically segregate into distinct domains to coordinate various cellular functions. The ability to manipulate the partitioning of specific membrane proteins without involving genetic modification is essential for decoding various cellular processes but highly challenging. In this work, by conjugating cholesterols or tocopherols at the three bottom vertices of the DNA tetrahedron, we develop two sets of nanodevices for the selective targeting of lipid-order (Lo) and lipid-disorder (Ld) domains on the live cell membrane. By incorporation of protein-recognition ligands, such as aptamers or antibodies, through toehold-mediated strand displacement, these DNA nanodevices enable dynamic translocation of target proteins between these two domains. We first used PTK7 as a protein model and demonstrated, for the first time, that the accumulation of PTK7 to the Lo domains could promote tumor cell migration, while sequestering it in the Ld domains would inhibit the movement of the cells. Next, based on their modular nature, these DNA nanodevices were extended to regulate the process of T cell activation through manipulating the translocation of CD45 between the Lo and the Ld domains. Thus, our work is expected to provide deep insight into the study of membrane structure and molecular interactions within diverse cell signaling processes.

Ultrasmall and photostable nanotheranostic agents based on carbon quantum dots passivated with polyamine-containing organosilane molecules.

In this work, we demonstrate that ultrasmall, photostable and multifunctional carbon quantum dots (or carbon dots, CDs) passivated with polyamine-containing organosilane molecules can realize simultaneous cell imaging and anticancer drug delivery. The presence of abundant surface amine groups makes these CDs be able to covalently link with the anticancer drug, doxorubicin (DOX), with an extremely high drug loading capacity (62.8%), while the surface hydroxyl groups ensure the good water-dispersibility of the CDs-DOX. Besides the use as a drug carrier, the fluorescent CDs also enable the dynamic tracing of the drug release process. When the CDs-DOX complexes were internalized by the human breast cancer cells (MCF-7), DOX could gradually detach from the surface of CDs and enter into the cell nucleus, while the CDs themselves still resided in the cytoplasm. In addition, the in vivo experiments showed that the CDs-DOX complexes exhibited a better tumor inhibition performance than free DOX molecules, which may be ascribed to the prolonged drug accumulation in tumor tissues. Furthermore, the as-synthesized CDs also exhibited negligible cytotoxicity/systemic side effects, and could successfully illuminate mammalian, bacterial and fungal cells, making them good candidates as not only drug delivery vehicles but also universal cell imaging reagents. The present work may have implications for the fabrication of functional carbon-based nanomaterials and foster the development of carbon dots as novel nanotheranostics for various biomedical applications.