Layer-by-layer nanoparticles with a pH-sheddable layer for in vivo targeting of tumor hypoxia

ACS Nano. 2011 Jun 28;5(6):4284-92. doi: 10.1021/nn200876f. Epub 2011 Apr 29.


Inspired by the simplicity and versatility of layer-by-layer (LbL) assembly, we applied multilayered polyelectrolyte assemblies on nanoparticles to create viable systemic delivery systems. Focusing on tumor-specific delivery, LbL nanoparticles that exhibit a pH-sensitive outer stealth layer are demonstrated to target and be retained in hypoxic tumor regions. The neutral layers shed in response to acidity to reveal a charged nanoparticle surface that is readily taken up by tumor cells. The first in vivo demonstration of this mechanism of targeting is presented, as well as an initial examination of the mechanism of uptake of the nanoparticles. We further demonstrate that this concept for tumor targeting is potentially valid for a broad range of cancers, with applicability for therapies that target hypoxic tumor tissue.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Electrolytes
  • Female
  • HeLa Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Hypoxia
  • Mice
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Nanotechnology / methods
  • Neoplasm Transplantation
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Surface Properties
  • Tetrazolium Salts / pharmacology
  • Thiazoles / pharmacology


  • Electrolytes
  • Tetrazolium Salts
  • Thiazoles
  • Polyethylene Glycols
  • thiazolyl blue