PEGylated dendritic polyglycerol conjugate targeting NCAM-expressing neuroblastoma: Limitations and challenges

Nanomedicine. 2018 Jun;14(4):1169-1179. doi: 10.1016/j.nano.2018.02.009. Epub 2018 Feb 20.


Neural cell adhesion molecule (NCAM) is found to be a stem-cell marker in several tumor types and its overexpression is known to correlate with increased metastatic capacity. To combine extravasation- and ligand-dependent targeting to NCAM overexpressing-cells in the tumor microenvironment, we developed a PEGylated NCAM-targeted dendritic polyglycerol (PG) conjugate. Here, we describe the synthesis, physico-chemical characterization and biological evaluation of a PG conjugate bearing the mitotic inhibitor paclitaxel (PTX) and an NCAM-targeting peptide (NTP). PG-NTP-PTX-PEG was evaluated for its ability to inhibit neuroblastoma progression in vitro and in vivo as compared to non-targeted derivatives and free drug. NCAM-targeted conjugate inhibited the migration of proliferating endothelial cells, suggesting it would be able to inhibit tumor angiogenesis. The targeting conjugate provided an improved binding and uptake on IMR-32 cells compared to non-targeted control. However, these results did not translate to our in vivo model on orthotopic neuroblastoma bearing mice.

Keywords: Neural cell adhesion molecule; Neuroblastoma; Paclitaxel; Polyglycerol; Polymer-drug conjugates; Polymeric nanomedicines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Delivery Systems / methods
  • Glycerol / chemistry*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Nanomedicine / methods
  • Neural Cell Adhesion Molecules / metabolism*
  • Neuroblastoma / metabolism*
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Polymers / chemistry*
  • Tumor Microenvironment


  • Neural Cell Adhesion Molecules
  • Peptides
  • Polymers
  • polyglycerol
  • Paclitaxel
  • Glycerol