Investigating the Cellular Specificity in Tumors of a Surface-Converting Nanoparticle by Multimodal Imaging

Bioconjug Chem. 2017 May 17;28(5):1413-1421. doi: 10.1021/acs.bioconjchem.7b00086. Epub 2017 May 5.


Active targeting of nanoparticles through surface functionalization is a common strategy to enhance tumor delivery specificity. However, active targeting strategies tend to work against long polyethylene glycol's shielding effectiveness and associated favorable pharmacokinetics. To overcome these limitations, we developed a matrix metalloproteinase-2 sensitive surface-converting polyethylene glycol coating. This coating prevents nanoparticle-cell interaction in the bloodstream, but, once exposed to matrix metalloproteinase-2, i.e., when the nanoparticles accumulate within the tumor interstitium, the converting polyethylene glycol coating is cleaved, and targeting ligands become available for binding to tumor cells. In this study, we applied a comprehensive multimodal imaging strategy involving optical, nuclear, and magnetic resonance imaging methods to evaluate this coating approach in a breast tumor mouse model. The data obtained revealed that this surface-converting coating enhances the nanoparticle's blood half-life and tumor accumulation and ultimately results in improved tumor-cell targeting. Our results show that this enzyme-specific surface-converting coating ensures a high cell-targeting specificity without compromising favorable nanoparticle pharmacokinetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Magnetic Resonance Imaging / methods*
  • Matrix Metalloproteinase 2 / chemistry
  • Matrix Metalloproteinase 2 / metabolism*
  • Mice
  • Mice, Nude
  • Multimodal Imaging / methods*
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Spectrophotometry, Infrared / methods*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • MMP2 protein, human
  • Matrix Metalloproteinase 2