EGFP-EGF1 protein-conjugated PEG-PLA nanoparticles for tissue factor targeted drug delivery

Biomaterials. 2010 Jul;31(21):5619-26. doi: 10.1016/j.biomaterials.2010.03.055. Epub 2010 Apr 21.

Abstract

In a strategy for anti-thrombotic therapy, we have expressed EGFP-EGF1 fusion protein, in which EGF1 can bind with tissue factor (TF). EGFP has previously been widely used as a fluorescent protein marker. EGFP-EGF1 protein was thiolated and conjugated to the malemide covering on the pegylated nanoparticles (NP) to form the EGFP-EGF1-NP. The EGFP-EGF1-NP was characterized in terms of morphology, size and zeta potential. In vitro cell viability experiment confirmed that the biodegradable EGFP-EGF1-NP was safe. To evaluate the delivering ability of EGFP-EGF1-NP, a fluorochrome dye, Dir, was incorporated into the nanoparticle, and the loading capacity and release property of the particle were examined. In vitro results showed that the binding ability of EGFP-EGF1-NP with TF-expressing cells was significantly stronger than that of non-conjugated NP. In vivo multispectral fluorescent imaging demonstrated that EGFP-EGF1-NP had high specificity and sensitivity in targeting thrombi. Our study demonstrated that EGFP-EGF1-NP is a promising TF-targeting drug delivery system for thrombolytic treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Carriers / chemistry*
  • Drug Carriers / metabolism
  • Drug Delivery Systems / methods
  • Factor VII / chemistry*
  • Factor VII / genetics
  • Factor VII / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Nanoparticles / chemistry*
  • Polyethylene Glycols / chemistry*
  • Protein Structure, Tertiary
  • Rats
  • Recombinant Fusion Proteins / chemistry*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Thromboplastin / metabolism*
  • Tissue Distribution

Substances

  • Drug Carriers
  • Recombinant Fusion Proteins
  • monomethoxypolyethyleneglycol-polylactide block copolymer
  • Green Fluorescent Proteins
  • Polyethylene Glycols
  • Factor VII
  • Thromboplastin