Folic acid-modified dendrimer-entrapped gold nanoparticles as nanoprobes for targeted CT imaging of human lung adencarcinoma

Biomaterials. 2013 Jan;34(2):470-80. doi: 10.1016/j.biomaterials.2012.09.054. Epub 2012 Oct 22.

Abstract

We report a new usage of folic acid-modified dendrimer-entrapped gold nanoparticles (Au DENPs-FA) as nanoprobes for in vitro and in vivo targeted computed tomography (CT) imaging of human lung adencarcinoma. In this study, Au DENPs prepared using amine-terminated generation 5 poly(amidoamine) dendrimers as templates were covalently linked with FA, followed by an acetylation reaction to neutralize the remaining dendrimer surface amines. The formed Au DENPs-FA was used for both in vitro and in vivo targeted CT imaging of human lung adencarcinoma cells (SPC-A1 cells) and the xenograft tumor model, which express folic acid receptors (FAR) verified by immunohistochemical staining. Micro-CT images show that SPC-A1 cells can be detected under X-ray after incubation with the Au DENPs-FA in vitro and the xenograft tumor model can be imaged after intravenous, intratumoral, and intraperitoneal administration of the particles. Transmission electron microscopy data confirm that the Au DENPs-FA is able to be uptaken dominantly in the lysosomes of the cells. Combined morphological observation of cells after Hematoxylin and Eosin staining, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay of cell viability, and flow cytometric analysis of cell cycle and apoptosis show that the Au DENPs-FA does not affect cell morphology, viability, and cell cycle and apoptosis, indicating their good biocompatibility at the given concentration range. These findings suggest that the developed Au DENPs-FA have a great potential to be used as imaging probes for targeted CT imaging of human lung adencarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma of Lung
  • Animals
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dendrimers* / chemistry
  • Dendrimers* / toxicity
  • Folic Acid* / chemistry
  • Folic Acid* / toxicity
  • Gold
  • Humans
  • Lung / pathology*
  • Lung Neoplasms / diagnosis*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles* / chemistry
  • Nanoparticles* / toxicity
  • Tomography, X-Ray Computed

Substances

  • Dendrimers
  • PAMAM Starburst
  • Gold
  • Folic Acid