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Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3391-3400. doi: 10.1073/pnas.1810764116. Epub 2019 Feb 11.

Quantitative zeptomolar imaging of miRNA cancer markers with nanoparticle assemblies.

Qu A1,2, Sun M1,2, Xu L1,2, Hao C1,2, Wu X1,2, Xu C1,2, Kotov NA3,4, Kuang H5,2.

Author information

1
State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.
2
International Joint Research Laboratory for Biointerface and Biodetection, Jiangnan University, Wuxi, Jiangsu 214122, China.
3
Department of Chemical Engineering, Biointerface Institute, University of Michigan, Ann Arbor, MI 48109; kuangh@jiangnan.edu.cn kotov@umich.edu.
4
Michigan Institute of Translational Nanotechnology, Ypsilanti, MI 48198.
5
State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; kuangh@jiangnan.edu.cn kotov@umich.edu.

Abstract

Multiplexed detection of small noncoding RNAs responsible for posttranscriptional regulation of gene expression, known as miRNAs, is essential for understanding and controlling cell development. However, the lifetimes of miRNAs are short and their concentrations are low, which inhibits the development of miRNA-based methods, diagnostics, and treatment of many diseases. Here we show that DNA-bridged assemblies of gold nanorods with upconverting nanoparticles can simultaneously quantify two miRNA cancer markers, namely miR-21 and miR-200b. Energy upconversion in nanoparticles affords efficient excitation of fluorescent dyes via energy transfer in the superstructures with core-satellite geometry where gold nanorods are surrounded by upconverting nanoparticles. Spectral separation of the excitation beam and dye emission wavelengths enables drastic reduction of signal-to-noise ratio and the limit of detection to 3.2 zmol/ngRNA (0.11 amol or 6.5 × 104 copies) and 10.3 zmol/ngRNA (0.34 amol or 2.1 × 105 copies) for miR-21 and miR-200b, respectively. Zeptomolar sensitivity and analytical linearity with respect to miRNA concentration affords multiplexed detection and imaging of these markers, both in living cells and in vivo assays. These findings create a pathway for the creation of an miRNA toolbox for quantitative epigenetics and digital personalized medicine.

KEYWORDS:

assembly; cancer; miRNA; nanoparticles; superstructures

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