The Binding Avidity of a Nanoparticle-Based Multivalent Targeted Drug Delivery Platform

Seungpyo Hong, Pascale R. Leroueil, István J. Majoros, Bradford G. Orr, James R. Baker, Mark M. Banaszak Holl

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Abstract

Dendrimer-based anticancer nanotherapeutics containing ∼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 (KD) between the nanodevices and FBP measured by SPR are dramatically enhanced through multivalency (∼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 KD, not an enhanced rate of endocytosis, is the key factor resulting in the improved biological targeting by these drug delivery platforms.

Original languageEnglish
Pages (from-to)107-115
Number of pages9
JournalChemistry and Biology
Volume14
Issue number1
DOIs
Publication statusPublished - 2007 Jan

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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    Hong, S., Leroueil, P. R., Majoros, I. J., Orr, B. G., Baker, J. R., & Banaszak Holl, M. M. (2007). The Binding Avidity of a Nanoparticle-Based Multivalent Targeted Drug Delivery Platform. Chemistry and Biology, 14(1), 107-115. https://doi.org/10.1016/j.chembiol.2006.11.015