NIR light-controlled DNA nanodevice for amplified mRNA imaging and precise gene therapy

Accurately delivering antisense oligonucleotides (ASOs) to tumor cells for gene therapy poses a significant challenge. To address this issue, we develop a NIR light-activable DNA nanodevice to target survivin mRNA and simultaneously release ASOs in tumor cells, which allows high-precision spatiotemp...

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Veröffentlicht in:Nano today 2024-02, Vol.54, p.102110, Article 102110
Hauptverfasser: Xiang, Miaomiao, Jiang, Yuelin, Zhou, Jiajia, Bao, Guochen, Luo, Xianzhu, Zhang, Le, Jin, Dayong, Xian, Yuezhong, Zhang, Cuiling
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Sprache:eng
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Zusammenfassung:Accurately delivering antisense oligonucleotides (ASOs) to tumor cells for gene therapy poses a significant challenge. To address this issue, we develop a NIR light-activable DNA nanodevice to target survivin mRNA and simultaneously release ASOs in tumor cells, which allows high-precision spatiotemporal imaging and efficient gene therapy. The concept is based on upconversion nanoparticles, which can convert NIR light into UV emissions to activate an entropy-driven DNA walking system for mRNA recognition in tumor cells. The intramolecular toehold-mediated entropy-driven catalytic reaction generates a large amount of Bcl-2 ASOs, which allows accurate delivery of ASOs for gene therapy due to the specific targeting of mRNA in tumor cells. The results from in vitro and in vivo experiments show that the NIR light-activated DNA nanodevice can detect mRNA with high sensitivity by DNA walking amplification and high precision in gene delivery. Moreover, the released ASOs from DNA walking system down-regulate the expression of Bcl-2 anti-apoptosis protein and induce tumor cell apoptosis, thereby suppressing tumor growth without a transfection reagent. The NIR-light-controlled DNA nanodevice holds great potential for precise gene therapy in clinical applications. [Display omitted] •The DNA nanodevice can be triggered by NIR light in living cells with the assistance of upconversion nanoparticles.•The DNA nanodevice can provide spatial and temporal resolution for mRNA imaging.•An abundant release of Bcl-2 OSA can be used for precise gene silencing in vivo.
ISSN:1748-0132
1878-044X
DOI:10.1016/j.nantod.2023.102110