mRNA-Activated Multifunctional DNAzyme Nanotweezer for Intracellular mRNA Sensing and Gene Therapy
| Autor: | Ting-Ting Chen, Juan Zhang, Mengyun He, Manman He, Jintao Yi, Cunpeng Nie, Xia Chu |
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| Rok vydání: | 2021 |
| Předmět: |
Materials science
Surface Properties Genetic enhancement Deoxyribozyme Apoptosis Biocompatible Materials 02 engineering and technology 010402 general chemistry 01 natural sciences chemistry.chemical_compound Survivin Tumor Cells Cultured Humans Nanotechnology Gene silencing General Materials Science Gene Silencing RNA Messenger Particle Size Drug Carriers Messenger RNA DNA Catalytic Genetic Therapy 021001 nanoscience & nanotechnology 0104 chemical sciences Cell biology chemistry Cancer cell 0210 nano-technology Intracellular DNA |
| Zdroj: | ACS Applied Materials & Interfaces. 13:8015-8025 |
| ISSN: | 1944-8252 1944-8244 |
| Popis: | Deoxyribozyme (DNAzyme) is regarded as a promising gene therapy drug. However, poor cellular uptake efficacy and low biological stability limit the utilization of DNAzyme in gene therapy. Here, we report a well-known programmable DNAzyme-based nanotweezer (DZNT) that provides a new strategy for the detection of TK1 mRNA and survivin mRNA-targeted gene silencing therapy. At the end of the DZNT arm, there are two functionalized single-stranded DNA and each consists of two parts: the segment complementary to TK1 mRNA and the split-DNAzyme segment. The hybridization with intracellular TK1 mRNA enables the imaging of TK1 mRNA. Meanwhile, the hybridization draws the split-DNAzyme close to each other and activates DNAzyme to cleave the survivin mRNA to realize gene silencing therapy. The results demonstrate that the DZNT nanocarrier has excellent cell penetration, good biocompatibility, and noncytotoxicity. DZNT can image intracellular biomolecule TK1 mRNA with a high contrast. Furthermore, the split-DNAzyme can efficiently cleave the survivin mRNA with the aid of TK1 mRNA commonly present in cancer cells, accordingly can selectively kill cancer cells, and has no harm to normal cells. Taken together, the multifunctional programmable DZNT provides a promising platform for the early diagnosis of tumors and gene therapy. |
| Databáze: | OpenAIRE |
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