Publications [#210140] of Mark W. Dewhirst

Papers Published

1. AJ Simnick, M Amiram, W Liu, G Hanna, MW Dewhirst, CD Kontos, A Chilkoti, In vivo tumor targeting by a NGR-decorated micelle of a recombinant diblock copolypeptide., Journal of controlled release : official journal of the Controlled Release Society, vol. 155 no. 2 (October, 2011), pp. 144-51, ISSN 1873-4995 [doi]
   (last updated on 2012/10/26)

   Abstract:
   Antivascular targeting is a promising strategy for tumor therapy. This strategy has the potential to overcome many of the transport barriers associated with targeting tumor cells in solid tumors, because the tumor vasculature is directly accessible to targeting vehicles in systemic circulation. We report a novel nanoscale delivery system consisting of multivalent polymer micelles to target receptors that are preferentially upregulated in the tumor vasculature and perivascular cells, specifically CD13. To this end we utilized amphiphilic block copolymers, composed of a genetically engineered elastin-like polypeptide (ELP) that self-assemble into monodisperse spherical micelles. These polymer micelles were functionalized by incorporating the NGR tripeptide ligand, which targets the CD13 receptor, on their corona. We examined the self-assembly and in vivo tumor targeting by these NGR-functionalized nanoparticles and show that multivalent presentation of NGR by micelle self-assembly selectively targets the tumor vasculature by targeting CD13. Furthermore, we show greater vascular retention and extravascular accumulation of nanoparticles in tumor tissue compared to normal tissue, although the enhancement is modest. These results suggest that enhanced delivery to solid tumors can be achieved by targeting upregulated receptors in the tumor vasculature with multivalent ligand-presenting nanoparticles, but additional work is required to optimize such systems for multivalent targeting.

   Keywords:
   Angiogenesis Inhibitors • Animals • Antigens, CD13 • Cell Line, Tumor • Drug Carriers • Elastin • Electrophoresis, Polyacrylamide Gel • Escherichia coli • Female • Humans • Hydrophobic and Hydrophilic Interactions • Ligands • Light • Mice • Mice, Nude • Micelles • Microscopy, Confocal • Microscopy, Fluorescence • Neovascularization, Pathologic • Oligopeptides • Peptides • Reverse Transcriptase Polymerase Chain Reaction • Scattering, Radiation • Temperature • Xenograft Model Antitumor Assays • administration & dosage* • chemistry • chemistry* • drug therapy* • genetics • metabolism • metabolism* • pathology • therapeutic use