Conductance-Based Biophysical Distinction and Microfluidic Enrichment of Nanovesicles Derived from Pancreatic Tumor Cells of Varying Invasiveness

Anal Chem. 2019 Aug 20;91(16):10424-10431. doi: 10.1021/acs.analchem.8b05745. Epub 2019 Aug 1.

Abstract

Diagnostics based on exosomes and other extracellular vesicles (EVs) are emerging as strategies for informing cancer progression and therapies, since the lipid content and macromolecular cargo of EVs can provide key phenotypic and genotypic information on the parent tumor cell and its microenvironment. We show that EVs derived from more invasive pancreatic tumor cells that express high levels of tumor-specific surface proteins and are composed of highly unsaturated lipids that increase membrane fluidity, exhibit significantly higher conductance versus those derived from less invasive tumor cells, based on dielectrophoresis measurements. Furthermore, through specific binding of the EVs to gold nanoparticle-conjugated antibodies, we show that these conductance differences can be modulated in proportion to the type as well as level of expressed tumor-specific antigens, thereby presenting methods for selective microfluidic enrichment and cytometry-based quantification of EVs based on invasiveness of their parent cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / analysis*
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism
  • Cell Communication
  • Cell Line, Tumor
  • Electric Conductivity
  • Electrophoresis
  • Extracellular Vesicles / chemistry*
  • Gold / chemistry
  • Heterografts
  • Humans
  • Male
  • Metal Nanoparticles / chemistry
  • Mice
  • Mice, Nude
  • Microfluidic Analytical Techniques
  • Neoplasm Invasiveness
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatic Neoplasms / chemistry*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Tumor Microenvironment / genetics

Substances

  • Antigens, Neoplasm
  • Neoplasm Proteins
  • Gold