Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer

Int J Nanomedicine. 2013:8:2589-600. doi: 10.2147/IJN.S46177. Epub 2013 Jul 19.

Abstract

Development of dual-mode or multi-mode imaging contrast agents is important for accurate and self-confirmatory diagnosis of cancer. We report a new multifunctional, dendrimer-based gold nanoparticle (AuNP) as a dual-modality contrast agent for magnetic resonance (MR)/computed tomography (CT) imaging of breast cancer cells in vitro and in vivo. In this study, amine-terminated generation 5 poly(amidoamine) dendrimers modified with gadolinium chelate (DOTA-NHS) and polyethylene glycol monomethyl ether were used as templates to synthesize AuNPs, followed by Gd(III) chelation and acetylation of the remaining dendrimer terminal amine groups; multifunctional dendrimer-entrapped AuNPs (Gd-Au DENPs) were formed. The formed Gd-Au DENPs were used for both in vitro and in vivo MR/CT imaging of human MCF-7 cancer cells. Both MR and CT images demonstrate that MCF-7 cells and the xenograft tumor model can be effectively imaged. The Gd-Au DENPs uptake, mainly in the cell cytoplasm, was confirmed by transmission electron microscopy. The cell cytotoxicity assay, cell morphology observation, and flow cytometry show that the developed Gd-Au DENPs have good biocompatibility in the given concentration range. Our results clearly suggest that the synthetic Gd-Au DENPs are amenable for dual-modality MR/CT imaging of breast cancer cells.

Keywords: CT imaging; MR imaging; PAMAM dendrimers; PEGylation; breast cancer cells; gadolinium; gold nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Survival / drug effects
  • Contrast Media / chemistry*
  • Contrast Media / pharmacokinetics
  • Contrast Media / toxicity
  • Dendrimers / chemistry*
  • Dendrimers / pharmacokinetics
  • Dendrimers / toxicity
  • Female
  • Heterografts
  • Humans
  • MCF-7 Cells
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mice
  • Mice, Nude
  • Molecular Imaging
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Succinimides / chemistry
  • Tissue Distribution
  • Tomography, X-Ray Computed / methods*

Substances

  • Contrast Media
  • DOTA-NHS
  • Dendrimers
  • Succinimides