Specificity and mobility of biomacromolecular, multivalent constructs for cellular targeting.
Effective targeting of drugs to cells requires that the drug reach the target cell and interact specifically with it. In this study, we synthesized a biomacromolecular, multivalent construct intended to target glioblastoma tumors. The construct was created by linking three dodecapeptides, reported to bind the alpha 6beta1 integrin, with poly(ethylene glycol) linkers. The construct is intended to be delivered locally, and it demonstrates a more homogeneous and more rapid perfusion profile in comparison with quantum dots. The binding specificity of the construct was investigated by using glioblastoma cells and normal human astrocyte cells. The results reveal qualitative differences in binding between glioma and normal human astrocyte cells, with a moderate increase in binding avidity due to multivalency (0.79 microM for the trivalent construct versus 4.28 microM for the dodecapeptide). Overall, biomacromolecular constructs appear to be a promising approach for targeting with high biocompatibility, good perfusion abilities, and specificity.
Rosca
Elena V
EV
Harrington Department of Bioengineering, Arizona State University, Tempe, Arizona 85287-9709, USA.
Stukel
Jill M
JM
Gillies
Robert J
RJ
Vagner
Josef
J
Caplan
Michael R
MR
D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D018390:Gene Targeting / Q000379:methods; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D014407:Tumor Cells, Cultured
D001672:Biocompatible Materials; D046911:Macromolecular Substances