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

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.
AuthorsHui Shi, Xiaoxiao He, Kemin Wang, Xu Wu, Xiaosheng Ye, Qiuping Guo, Weihong Tan, Zhihe Qing, Xiaohai Yang, Bing Zhou
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 108 Issue 10 Pg. 3900-5 (Mar 08 2011) ISSN: 1091-6490 [Electronic] United States
PMID21368158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Aptamers, Nucleotide
  • DNA Probes
  • Membrane Proteins
Topics
  • Aptamers, Nucleotide
  • Base Sequence
  • Cell Line
  • DNA Probes
  • Flow Cytometry
  • Humans
  • Membrane Proteins (chemistry, metabolism)
  • Neoplasms (metabolism, pathology)
  • Protein Conformation
  • Spectrometry, Fluorescence

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