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

doi:10.1016/j.chembiol.2006.11.015

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

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

486 Citations (Scopus)

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 (K_D) 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 K_D, not an enhanced rate of endocytosis, is the key factor resulting in the improved biological targeting by these drug delivery platforms.

Original language	English
Pages (from-to)	107-115
Number of pages	9
Journal	Chemistry and Biology
Volume	14
Issue number	1
DOIs	https://doi.org/10.1016/j.chembiol.2006.11.015
Publication status	Published - 2007 Jan

Bibliographical note

Funding Information:
This work has been funded with federal funds from the National Cancer Institute, National Institutes of Health, under contract # N01-CO-27173. This research has been also supported by State of Michigan MEDC funding under GR-472, grant # 085P3000548. The University of Michigan has licensed this technology to a start-up company, Avidimer Therapeutics, and Dr. Baker has a significant equity position in this entity. The authors thank Ankur Desai for his assistance with GPC measurements.

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.chembiol.2006.11.015

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title = "The Binding Avidity of a Nanoparticle-Based Multivalent Targeted Drug Delivery Platform",

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.",

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note = "Funding Information: This work has been funded with federal funds from the National Cancer Institute, National Institutes of Health, under contract # N01-CO-27173. This research has been also supported by State of Michigan MEDC funding under GR-472, grant # 085P3000548. The University of Michigan has licensed this technology to a start-up company, Avidimer Therapeutics, and Dr. Baker has a significant equity position in this entity. The authors thank Ankur Desai for his assistance with GPC measurements. ",

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AU - Baker, James R.

AU - Banaszak Holl, Mark M.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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