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Issue 27, 2020
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Biomineralized metal–organic framework nanoparticles enable a primer exchange reaction-based DNA machine to work in living cells for imaging and gene therapy

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Abstract

Sensitive tumor imaging and precise tumor therapy play critical roles in the cancer combat. Herein, we build a DNA machine based on a primer exchange reaction (PER) for mRNA imaging and gene therapy. By using zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) to co-deliver the components including a primer, hairpin and strand displacing polymerase to the living cells, the PER-based DNA machine can be initiated by intracellular survivin mRNA and continuously produce Bcl-2 antisense DNA (ASD), which enables the DNA machine not only to image survivin mRNA but also to implement gene therapy. The results demonstrate that ZIF-8 NPs can protect the polymerases and nucleic acid probes from protease attack and nuclease degradation. After internalization, pH-responsive ZIF-8 NPs can efficiently release cargos from endo-lysosomes due to the protonation effect. The intracellular PER-based DNA machine has been demonstrated to be able to sensitively image survivin mRNA expression levels and selectively kill the cancer cells and has no effect on the normal cells. The PER-based DNA machine may provide a promising platform for early stage tumor diagnosis and more precise tumor therapy.

Graphical abstract: Biomineralized metal–organic framework nanoparticles enable a primer exchange reaction-based DNA machine to work in living cells for imaging and gene therapy

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Supplementary files

Article information


Submitted
18 Jan 2020
Accepted
16 Jun 2020
First published
16 Jun 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 7092-7101
Article type
Edge Article

Biomineralized metal–organic framework nanoparticles enable a primer exchange reaction-based DNA machine to work in living cells for imaging and gene therapy

J. Zhang, M. He, C. Nie, M. He, Q. Pan, C. Liu, Y. Hu, T. Chen and X. Chu, Chem. Sci., 2020, 11, 7092
DOI: 10.1039/D0SC00339E

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