Oligonucleotide-coated metallic nanoparticles as a flexible platform for molecular imaging agents

Nitin Nitin, David J. Javier, Rebecca Richards-Kortum

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Targeted metallic nanoparticles have shown promise as contrast agents for molecular imaging. To obtain molecular specificity, the nanoparticle surface must be appropriately functionalized with probe molecules that will bind to biomarkers of interest. The aim of this study was to develop and characterize a flexible approach to generate molecular imaging agents based on gold nanoparticles conjugated to a diverse range of probe molecules. We present two complementary oligonucleotide-based approaches to develop gold nanoparticle contrast agents which can be functionalized with a variety of biomolecules ranging from small molecules, to peptides, to antibodies. The size, biocompatibility, and protein concentration per nanoparticle are characterized for the two oligonucleotide-based approaches; the results are compared to contrast agents prepared using adsorption of proteins on gold nanoparticles by electrostatic interaction. Contrast agents prepared from oligonucleotide- functionalized nanoparticles are significantly smaller in size and more stable than contrast agents prepared by adsorption of proteins on gold nanoparticles. We demonstrate the flexibility of the oligonucleotide-based approach by preparing contrast agents conjugated to folate, EGF peptide, and anti-EGFR antibodies. Reflectance images of cancer cell lines labeled with functionalized contrast agents show significantly increased image contrast which is specific for the target biomarker. To demonstrate the modularity of this new bioconjugation approach, we use it to conjugate both fluorophore and anti-EGFR antibodies to metal nanoparticles, yielding a contrast agent which can be probed with multiple imaging modalities. This novel bioconjugation approach can be used to prepare contrast agents targeted with biomolecules that span a diverse range of sizes; at the same time, the bioconjugation method can be adapted to develop multimodal contrast agents for molecular imaging without changing the coating design or material.

Original languageEnglish (US)
Pages (from-to)2090-2096
Number of pages7
JournalBioconjugate Chemistry
Volume18
Issue number6
DOIs
StatePublished - Nov 2007
Externally publishedYes

Fingerprint

Metal Nanoparticles
Molecular imaging
Molecular Imaging
Oligonucleotides
Contrast Media
Nanoparticles
Gold
Antibodies
Biomolecules
Biomarkers
Proteins
Adsorption
Molecules
Anti-Idiotypic Antibodies
Peptides
Fluorophores
Metal nanoparticles
Coulomb interactions
Static Electricity
Biocompatibility

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Oligonucleotide-coated metallic nanoparticles as a flexible platform for molecular imaging agents. / Nitin, Nitin; Javier, David J.; Richards-Kortum, Rebecca.

In: Bioconjugate Chemistry, Vol. 18, No. 6, 11.2007, p. 2090-2096.

Research output: Contribution to journalArticle

Nitin, Nitin ; Javier, David J. ; Richards-Kortum, Rebecca. / Oligonucleotide-coated metallic nanoparticles as a flexible platform for molecular imaging agents. In: Bioconjugate Chemistry. 2007 ; Vol. 18, No. 6. pp. 2090-2096.
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