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Research Article

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

Hui Shi, Xiaoxiao He, Kemin Wang, Xu Wu, Xiaosheng Ye, Qiuping Guo, Weihong Tan, Zhihe Qing, Xiaohai Yang, and Bing Zhou
PNAS March 8, 2011 108 (10) 3900-3905; https://doi.org/10.1073/pnas.1016197108
Hui Shi
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Xiaoxiao He
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Kemin Wang
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  • For correspondence: kmwang@hnu.cn
Xu Wu
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Xiaosheng Ye
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Qiuping Guo
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Weihong Tan
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Zhihe Qing
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Xiaohai Yang
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Bing Zhou
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  1. Edited by Larry Gold, SomaLogic, Inc., Boulder, CO, and approved January 21, 2011 (received for review October 29, 2010)

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Abstract

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

Footnotes

  • Author contributions: H.S., X.H., and K.W. designed research; H.S., X.W., and X. Ye performed research; H.S., X.H., K.W., W.T., and X. Yang analyzed data; Q.G., Z.Q., and B.Z. contributed new reagents/analytic tools; and H.S., X.H., K.W., and W.T. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1016197108/-/DCSupplemental.

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Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration
Hui Shi, Xiaoxiao He, Kemin Wang, Xu Wu, Xiaosheng Ye, Qiuping Guo, Weihong Tan, Zhihe Qing, Xiaohai Yang, Bing Zhou
Proceedings of the National Academy of Sciences Mar 2011, 108 (10) 3900-3905; DOI: 10.1073/pnas.1016197108

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Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration
Hui Shi, Xiaoxiao He, Kemin Wang, Xu Wu, Xiaosheng Ye, Qiuping Guo, Weihong Tan, Zhihe Qing, Xiaohai Yang, Bing Zhou
Proceedings of the National Academy of Sciences Mar 2011, 108 (10) 3900-3905; DOI: 10.1073/pnas.1016197108
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