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Chem Biol. 2007 Jan;14(1):107-15.

The binding avidity of a nanoparticle-based multivalent targeted drug delivery platform.

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  • 1Program in Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA.

Abstract

Dendrimer-based anticancer nanotherapeutics containing approximately 5 folate molecules have shown in vitro and in vivo efficacy in cancer cell targeting. Multivalent interactions have been inferred from observed targeting efficacy, but have not been experimentally proven. This study provides quantitative and systematic evidence for multivalent interactions between these nanodevices and folate-binding protein (FBP). A series of the nanodevices were synthesized by conjugation with different amounts of folate. Dissociation constants (K(D)) between the nanodevices and FBP measured by SPR are dramatically enhanced through multivalency ( approximately 2,500- to 170,000-fold). Qualitative evidence is also provided for a multivalent targeting effect to KB cells using flow cytometry. These data support the hypothesis that multivalent enhancement of K(D), not an enhanced rate of endocytosis, is the key factor resulting in the improved biological targeting by these drug delivery platforms.

PMID:
17254956
[PubMed - indexed for MEDLINE]
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