Dynamically Monitoring the Clonal Evolution of Lung Cancer Based on the Molecular Characterization of Circulating Tumor Cells Using Aptamer Cocktail-Modified Nanosubstrates

ACS Appl Mater Interfaces. 2020 Feb 5;12(5):5671-5679. doi: 10.1021/acsami.9b22234. Epub 2020 Jan 27.

Abstract

Dynamically monitoring the clonal evolution of lung cancer and performing molecular analyses on tumor cells are challenging but necessary tasks to adjust therapeutic interventions and evaluate treatment efficacy. Circulating tumor cells (CTCs), as a "liquid biopsy", may offer an auxiliary tool to identify phenotypic transformation of solid tumors at primary or metastatic sites and uncover their corresponding molecular variation. Herein, we developed an aptamer-modified PEG-PLGA-nanofiber (PPN) microfluidic system optimized for recognizing rare CTC subtypes in lung cancer patients. This unique purification system can be adopted to monitor the clonal evolution of solid tumors by following the intrinsic immunophenotypes of CTCs, while significantly enhancing capture efficiency for polyclonal-derived tumor cells, further facilitating therapeutic evaluation via dynamic CTC enumeration. Combining with downstream single-cell sequencing, the aptamer-modified-PPN microfluidic system was able to provide early insight into tumor heterogeneity and predict histologic transformation in advance, broadening its clinical applications in lung cancer patients.

Keywords: aptamer; circulating tumor cells; clonal evolution; liquid biopsy; nanomaterials; nonsmall-cell lung cancer.

MeSH terms

  • Animals
  • Aptamers, Nucleotide / genetics*
  • Cell Line, Tumor
  • Clonal Evolution / genetics*
  • Humans
  • Liquid Biopsy / instrumentation
  • Liquid Biopsy / methods
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Mice
  • Microfluidic Analytical Techniques / instrumentation
  • Microfluidic Analytical Techniques / methods
  • Nanofibers / chemistry*
  • Neoplastic Cells, Circulating / pathology*
  • Polyesters / chemistry
  • Polyethylene Glycols / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • Aptamers, Nucleotide
  • Polyesters
  • polyethylene glycol-poly(lactide-co-glycolide)
  • Polyethylene Glycols