Cellular Uptake and Intra-Organ Biodistribution of Functionalized Silica-Coated Gold Nanorods

Mol Imaging Biol. 2016 Oct;18(5):667-76. doi: 10.1007/s11307-016-0938-9.

Abstract

Purpose: To develop a new nanobiosystem based on folate-functionalized silica-coated gold nanorods and to investigate its cellular uptake and intra-organ biodistribution in vitro and in vivo.

Procedures: Ellipsoidal silica-coated gold nanorods (GNRs@SIO2) were prepared by seeded growth method using silicon dioxide (SIO2) as the shell material. Rhodamine-labeled GNRs@SiO2-folic acid (FA) were obtained by reacting the amino group located on GNRs@SiO2-FA with rhodamine isothiocyanate. The characteristics of the prepared GNRs@SiO2-FA were studied using transmission electron microscopy (TEM) and UV spectra. The 3-[4, 5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) colorimetric method was used to assess the biocompatibility of GNRs@SiO2-FA, and their uptake into cells was observed using TEM. In vivo experiments of cellular uptake and study of the intra-organ biodistribution of GNRs@SiO2-FA were detected using intrinsic two-photon luminescence.

Results: Analysis of UV spectra confirmed the successfu1 preparation of GNRs@SiO2-FA. Results of the MTT assay demonstrated that surface modification of GNRs@SiO2-FA resulted in excellent biocompatibility. TEM examination revealed that GNRs@SiO2-FA entered the cells via endocytosis, which could connect to cancer cells with high folic acid expression. We found that GNRs exhibit bright luminescence and could be visualized in vivo by direct imaging of these particles within the tissue. Additionally, GNRs@SiO2-FA could specifically bind to tumor cells. GNRs@SiO2-FA entered tumor cells within 24 h and had a heterogeneous distribution with higher accumulation at the tumor cytoplasm.

Conclusion: GNRs@SiO2-FA can bind to cells and were found to be internalized by targeted folate receptor-expressing cells via a ligand-receptor-mediated endocytosis pathway, which is very useful in diagnosing diseases as well as in treating neoplasm with I-125 particles.

Keywords: Folic acid; Gold nanorods; SiO2; Two-photon-induced photoluminescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Disease Models, Animal
  • Endocytosis*
  • Folic Acid / metabolism
  • Gold / metabolism*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / pathology
  • Luminescence
  • Male
  • Nanotubes / chemistry*
  • Nanotubes / ultrastructure
  • Photons
  • Rabbits
  • Silicon Dioxide / metabolism*
  • Spectrometry, X-Ray Emission
  • Tissue Distribution
  • Tomography, X-Ray Computed

Substances

  • Gold
  • Silicon Dioxide
  • Folic Acid