The preferential homing of a platelet derived growth factor receptor-recognizing macromolecule to fibroblast-like cells in fibrotic tissue

Biochem Pharmacol. 2003 Oct 1;66(7):1307-17. doi: 10.1016/s0006-2952(03)00445-3.


Platelet derived growth factor (PDGF) is a key factor in the induction and progression of fibrotic diseases with the activated fibroblast as its target cell. Drug targeting to the PDGF-receptor is explored as a new approach to treat this disease. Therefore, we constructed a macromolecule with affinity for the PDGF-beta receptor by modification of albumin with a small peptide that recognises this PDGF-beta receptor. The binding of the peptide-modified albumin (pPB-HSA) to the PDGF-beta receptor was confirmed in competition studies with PDGF-BB using NIH/3T3-fibroblasts and activated hepatic stellate cells. Furthermore, pPB-HSA was able to reduce PDGF-BB-induced fibroblast proliferation in vitro, and proved to be devoid of proliferation-inducing activity itself. We assessed the distribution of pPB-HSA in vivo in two models of fibrosis and related the distribution of pPB-HSA to PDGF-beta receptor density. In rats with liver fibrosis (bile duct ligation model), pPB-HSA quickly accumulated in the liver in contrast to unmodified HSA (P<0.001). The major part of pPB-HSA in the fibrotic liver was localized in hepatic stellate cells. In rats with renal fibrosis (anti-Thy1.1 model), pPB-HSA also homed to the cells that expressed the PDGF-beta receptor, i.e. the mesangial cells in the glomeruli of the kidney. These results indicate that pPB-HSA may be applied as a macromolecular drug-carrier that accumulates specifically in cells expressing the PDGF-beta receptor, thus allowing a selective delivery of anti-fibrotic agents to these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Division / drug effects
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibrosis / pathology
  • Humans
  • Liver Cirrhosis / pathology*
  • Male
  • Mice
  • Rats
  • Rats, Wistar
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism*
  • Receptor, Platelet-Derived Growth Factor beta / metabolism*
  • Serum Albumin / metabolism*
  • Serum Albumin / pharmacology


  • Serum Albumin
  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptor, Platelet-Derived Growth Factor beta