A quantitative assessment of nanoparticle-ligand distributions: Implications for targeted drug and imaging delivery in dendrimer conjugates

Douglas G. Mullen, Ming Fang, Ankur Desai, James R. Baker, Bradford G. Orr, Mark M. Banaszak Holl

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121 Citations (Scopus)

Abstract

Functional nanoparticles often contain ligands including targeting molecules, fluorophores, and/or active moieties such as drugs. Characterizing the number of these ligands bound to each particle and the distribution of nanoparticle-ligand species is important for understanding the nanomaterial's function. In this study, the amide coupling methods commonly used to conjugate ligands to poly(amidoamine) (PAMAM) dendrimers were examined. A skewed Poisson distribution was observed and quantified using HPLC for two sets of dendrimer-ligand samples prepared using the amine-terminated form of the PAMAM dendrimer and a partially acetylated form of the PAMAM dendrimer that has been used for targeted in vivo drug delivery. The prepared samples had an average number of ligands per dendrimer ranging from 0.4 to 13. Distributions identified by HPLC are in excellent agreement with the mean ligand/dendrimer ratio, measured by 1H NMR, gel permeation chromatography (GPC), and potentiometric titration. These results provide insight into the heterogeneity of distributions that are obtained for many classes of nanomaterials to which ligands are conjugated and belie the use of simple cartoon models that present the "average" number of ligands bound as a physically meaningful representation for the material.

Original languageEnglish
Pages (from-to)657-670
Number of pages14
JournalACS Nano
Volume4
Issue number2
DOIs
Publication statusPublished - 23 Feb 2010
Externally publishedYes

Keywords

  • Drug delivery
  • Ligand distribution
  • Nanoparticle characterization
  • Nanotechnology
  • PAMAM dendrimer

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