Label-free visualization of nilotinib-functionalized gold nanoparticles within single mammalian cells by C60- SIMS imaging

Anal Bioanal Chem. 2017 May;409(12):3067-3076. doi: 10.1007/s00216-017-0262-5. Epub 2017 Mar 10.

Abstract

Obtaining a comprehensive grasp of the behavior and interaction of pharmaceutical compounds within single cells provides some of the fundamental details necessary for more effective drug development. In particular, the changes ensuing in the carrier, drug, and host environment in targeted drug therapy applications must be explored in greater detail, as these are still not well understood. Here, nilotinib-functionalized gold nanoparticles are examined within single mammalian cells with use of imaging cluster secondary ion mass spectrometry in a model study designed to enhance our understanding of what occurs to these particles once that have been internalized. Nilotinib, several types of gold nanoparticles, and the functionalized combination of the two were surveyed and successfully imaged within single cells to determine uptake and performance. Both nilotinib and the gold particle are able to be distinguished and visualized in the functionalized nanoparticle assembly within the cell. These compounds, while both internalized, do not appear to be present in the same pixels of the chemical image, indicating possible cleavage of nilotinib from the particle after cell uptake. The method provided in this work is a direct measurement of uptake and subcellular distribution of an active drug and its carrier within a framework. The results obtained from this study have the potential to be applied to future studies to provide more effective and specific cellular delivery of a relevant pharmaceutical compound.

Keywords: Gold nanoparticles; Nilotinib; Secondary ion mass spectrometry; Targeted drug therapy.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics*
  • Drug Carriers / analysis*
  • Drug Delivery Systems
  • Gold / analysis*
  • Metal Nanoparticles / analysis*
  • Mice
  • Particle Size
  • Pyrimidines / administration & dosage
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacokinetics*
  • RAW 264.7 Cells
  • Spectrometry, Mass, Secondary Ion / methods*

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Pyrimidines
  • Gold
  • nilotinib