A Nucleolin-Targeted Multimodal Nanoparticle Imaging Probe for Tracking Cancer Cells Using an Aptamer

Hwang, Do Won; Ko, Heung Kyu; Lee, Jung Hwan; Kang, Hyungu; Ryu, Sung Ho; Song, In Chan; Lee, Dong Hoon; Kim, Soonhag

doi:10.2967/jnumed.109.069880

Cited by 266 publications

(137 citation statements)

References 22 publications

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“…Various signal reporters have been adopted, including radioactive, magnetic, and fluorescent agents (9)(10)(11)(12)(13). Our group has demonstrated that near-infrared dye-labeled aptamers could effectively recognize cancer cells in vivo and achieve cancer imaging with high specificity (13).…”

mentioning

confidence: 99%

Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration

Shi

He²,

Wang³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

285

227

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Aptamers have emerged as promising molecular probes for in vivo cancer imaging, but the reported "always-on" aptamer probes remain problematic because of high background and limited contrast. To address this problem, we designed an activatable aptamer probe (AAP) targeting membrane proteins of living cancer cells and achieved contrast-enhanced cancer visualization inside mice. The AAP displayed a quenched fluorescence in its free state and underwent a conformational alteration upon binding to target cancer cells with an activated fluorescence. As proof of concept, in vitro analysis and in vivo imaging of CCRF-CEM cancer cells were performed by using the specific aptamer, sgc8, as a demonstration. It was confirmed that the AAP could be specifically activated by target cancer cells with a dramatic fluorescence enhancement and exhibit improved sensitivity for CCRF-CEM cell analysis with the cell number of 118 detected in 200 μl binding buffer. In vivo studies demonstrated that activated fluorescence signals were obviously achieved in the CCRF-CEM tumor sites in mice. Compared to always-on aptamer probes, the AAP could substantially minimize the background signal originating from nontarget tissues, thus resulting in significantly enhanced image contrast and shortened diagnosis time to 15 min. Furthermore, because of the specific affinity of sgc8 to target cancer cells, the AAP also showed desirable specificity in differentiating CCRF-CEM tumors from Ramos tumors and nontumor areas. The design concept can be widely adapted to other cancer cell-specific aptamer probes for in vivo molecular imaging of cancer.switchable aptamer probe | in vivo imaging | activatable fluorescent molecular imaging | cancer detection | cell surface protein

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mentioning

confidence: 99%

Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration

Shi

He²,

Wang³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

285

227

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“…Magnetic SNPs can be integrated with optical reporters for simultaneous cellular imaging and bioseparation, both for in vivo and in vitro applications (Corr et al, 2008;Hwang et al, 2010;Kim et al, 2008;Salgueiriño-Maceira et al, 2006). Likewise, paramagnetic iron oxide NPs and QDs can be embedded within the same polymeric matrix (Figure 7).…”

Section: Multifunctional Polymeric Npsmentioning

confidence: 99%

Polymeric nanoparticles for optical sensing

Canfarotta

Whitcombe

Piletsky

2013

Biotechnology Advances

121

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Nanotechnology is a powerful tool for use in diagnostic applications. For these purposes a variety of functional nanoparticles containing fluorescent labels, gold and quantum dots at their cores have been produced, with the aim of enhanced sensitivity and multiplexing capabilities. This work will review progress in the application of polymeric nanoparticles in optical diagnostics, both for in vitro and in vivo detection, together with a discussion of their biodistribution and biocompatibility.

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“…The developed probe was applied in cell culture to image nucleolin-expressed C6 glioma cells by fluorescence microscopy. In vivo imaging of the tumor model in nude mice was also achieved by scintigraphy with 67 Ga as a reporter and by MRI imaging with cobalt ferrite as a reporter (Hwang do et al, 2010).…”

Section: Multiplex Imagingmentioning

confidence: 99%

“…Ga have been used as reporters for 2D-scintigraphy (Charlton et al, 1997;Hicke et al, 2006;Hwang do et al, 2010).…”

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confidence: 99%

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Aptamer-based molecular imaging

Wang

Ray

2012

Protein Cell

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Molecular imaging has greatly advanced basic biology and translational medicine through visualization and quantification of single/multiple molecular events temporally and spatially in a cellular context and in living organisms. Aptamers, short single-stranded nucleic acids selected in vitro to bind a broad range of target molecules avidly and specifically, are ideal molecular recognition elements for probe development in molecular imaging. This review summarizes the current state of aptamer-based biosensor development (probe design and imaging modalities) and their application in imaging small molecules, nucleic acids and proteins mostly in a cellular context with some animal studies. The article is concluded with a brief discussion on the perspective of aptamer-based molecular imaging.

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A Nucleolin-Targeted Multimodal Nanoparticle Imaging Probe for Tracking Cancer Cells Using an Aptamer

Cited by 266 publications

References 22 publications

Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration

Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration

Polymeric nanoparticles for optical sensing

Aptamer-based molecular imaging

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