Building Electromagnetic Hot Spots in Living Cells via Target

Building Electromagnetic Hot Spots in Living Cells via Target-Triggered Nanoparticle Dimerization Wen Zhou,†,‡ Qiang Li,† Huiqiao Liu,† Jie Yang,† and Dingbin Liu*,†,‡ †

College of Chemistry, Research Center for Analytical Sciences, State Key Laboratory of Medicinal Chemical Biology, and Tianjin Key Laboratory of Molecular Recognition and Biosensing, Nankai University, Tianjin 300071, China ‡ Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China S Supporting Information *

ABSTRACT: Electromagnetic hot spots of surface-enhanced Raman scattering have been extensively employed for bioanalysis in solution or on a substrate, but building hot spots in living systems for probing targets of interest has not been achieved yet because of the complex and dynamic physiological environment. Herein, we show that a target-programmed nanoparticle dimerization can be combined with the background-free Raman reporters (alkyne, CC; nitrile, CN) for multiplexed imaging of microRNAs (miRNAs) in living cells. The in situ formation of plasmonic dimers results in an intense hot spot, thus dramatically enhancing the Raman signals of the reporters residing in the hot spot. More significantly, the reporters exhibit single nonoverlapping peaks in the cellular Ramansilent region (1800−2800 cm−1), thus eliminating spectral unmixing and background interference. A 3D Raman mapping technique was harnessed to monitor the spatial distribution of the dimers and thus the multiple miRNAs in cells. This approach could be extended to probe other biomarkers of interest for monitoring specific pathophysiological events at the live-cell level. KEYWORDS: surface-enhanced Raman scattering, hot spots, molecular imaging, microRNAs, nanoparticle assembly

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analytes and Raman reporters (RRs) show multiple peaks in the fingerprint region (