An Acidic-Microenvironment-Driven DNA Nanomachine Enables Specific ATP Imaging in the Extracellular Milieu of Tumor

Zhenghan Di, Jian Zhao, Hongqian Chu, Wenting Xue, Yuliang Zhao, Lele Li

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Extracellular ATP is an emerging target for cancer treatment because it is a key messenger for shaping the tumor microenvironment (TME) and regulating tumor progression. However, it remains a great challenge to design biochemical probes for targeted imaging of extracellular ATP in the TME. A TME-driven DNA nanomachine (Apt-LIP) that permits spatially controlled imaging of ATP in the extracellular milieu of tumors with ultrahigh signal-to-background ratio is reported. It operates in response to the mild acidity in the TME with the pH (low) insertion peptide (pHLIP) module, thus allowing the specific anchoring of the structure-switching signaling aptamer unit to the membrane of tumor cells for “off–on” fluorescence imaging of the extracellular ATP. Apt-LIP allows for acidity driven visualization of different extracellular concentrations of exogenous ATP, as well as the monitoring of endogenous ATP release from cells. Furthermore, it is demonstrated that Apt-LIP represents a promising platform for the specific imaging of the extracellular ATP in both primary and metastatic tumors. Ultimately, since diverse aptamers are obtained through in vitro selection, this design strategy can be further applied for precise detection of various extracellular targets in the TME.

Original languageEnglish (US)
Article number1901885
JournalAdvanced Materials
Volume31
Issue number33
DOIs
StatePublished - Aug 2019

Keywords

  • DNA nanomachines
  • cancer treatment
  • extracellular ATP
  • imaging
  • tumor microenvironment

ASJC Scopus subject areas

  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering

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