Self-assembled peptide nanoparticles as tumor microenvironment activatable probes for tumor targeting and imaging

J Control Release. 2014 Mar 10;177:11-9. doi: 10.1016/j.jconrel.2013.12.037. Epub 2014 Jan 10.


Design of specific and sensitive imaging probes for targeting tumor microenvironment holds great promise to achieve precise detection and rapid responsiveness to neoplastic tissues. Dysregulated pH, one of the most remarkable hallmarks of tumor microenvironment, can be considered as a good specific trigger for the design of broad-spectrum and local-environment responsive imaging probes. However, the current existing design strategies for pH-responsive systems are insufficient to meet the needs for a rapid and tumor-specific diagnosis. Here we reported a novel biomimetic nanostructure based on oligopeptide self-assembly that can quickly switch into dissociated stage with active fluorescence property from self-assembled stage with quenched fluorescence activity when encountering a subtle pH-change in tumor microenvironment (pH 6.8 vs. 7.4). This oligopeptide-assembly is examined as tumor microenvironment activatable probes for both intratumoral and intravenous in vivo tumor imaging. Through the distinct fluorescent intensities, it is validated that the acidic tumor microenvironment can activate stronger fluorescence signals. The tailor-made self-assembled oligopeptide nanomaterials have the potential for efficient and specific in situ diagnosis of various solid tumors with a weakly acidic microenvironment, which is expected to be of crucial importance for clinical tumor diagnostics.

Keywords: Peptides; Self-assembly; Tumor imaging; Tumor microenvironment; pH-sensitive activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholesterol / chemistry
  • Drug Delivery Systems
  • Fluorescent Dyes / chemistry
  • Melanoma, Experimental / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron, Transmission
  • Molecular Imaging
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Oligopeptides / administration & dosage*
  • Oligopeptides / chemistry
  • Skin Neoplasms / metabolism*
  • Tumor Microenvironment


  • Fluorescent Dyes
  • Oligopeptides
  • Cholesterol