PEGylated dendritic polyglycerol conjugate targeting NCAM-expressing neuroblastoma: Limitations and challenges |
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Authors: | Laura Isabel Vossen Ela Markovsky Anat Eldar-Boock Harald Rune Tschiche Stefanie Wedepohl Evgeny Pisarevsky Ronit Satchi-Fainaro Marcelo Calderón |
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Institution: | 1. Freie Universität Berlin, Institute of Chemistry and Biochemistry, Takustrasse 3, Berlin, Germany;2. Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel |
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Abstract: | 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. |
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Keywords: | Neuroblastoma Neural cell adhesion molecule Polyglycerol Polymeric nanomedicines Paclitaxel Polymer-drug conjugates |
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