Modular protein-DNA hybrid nanostructures as a drug delivery platform
| Autor: | Bo Am Seo, Joong-jae Lee, Yiseul Ryu, Yunjin Song, Jonghwi Beak, Cheol Am Hong, Hak-Sung Kim |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Exonuclease
02 engineering and technology 010402 general chemistry 01 natural sciences chemistry.chemical_compound Drug Delivery Systems Neoplasms DNA origami Humans General Materials Science Cytotoxicity Zinc finger biology PTEN Phosphohydrolase Zinc Fingers DNA 021001 nanoscience & nanotechnology 0104 chemical sciences Cell biology Nanostructures DNA-Binding Proteins chemistry Cancer cell Drug delivery biology.protein MCF-7 Cells 0210 nano-technology Molecular probe |
| Zdroj: | Nanoscale. 12(8) |
| ISSN: | 2040-3372 |
| Popis: | With the increasing number of identified intracellular drug targets, cytosolic drug delivery has gained much attention. Despite advances in synthetic drug carriers, however, construction of homogeneous and biocompatible nanostructures in a controllable manner still remains a challenge in a translational medicine. Herein, we present the modular design and assembly of functional DNA nanostructures through sequence-specific interactions between zinc-finger proteins (ZnFs) and DNA as a cytosolic drug delivery platform. Three kinds of DNA-binding ZnF domains were genetically fused to various proteins with different biological roles, including targeting moiety, molecular probe, and therapeutic cargo. The engineered ZnFs were employed as distinct functional modules, and incorporated into a designed ZnF-binding sequence of a Y-shaped DNA origami (Y-DNA). The resulting functional Y-DNA nanostructures (FYDN) showed self-assembled superstructures with homogeneous morphology, strong resistance to exonuclease activity and multi-modality. We demonstrated the general utility of our approach by showing efficient cytosolic delivery of PTEN tumour suppressor protein to rescue unregulated kinase signaling in cancer cells with negligible nonspecific cytotoxicity. |
| Databáze: | OpenAIRE |
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