A novel electrochemiluminescent cytosensor using dual-target magnetic probe recognition and nanozymes-catalyzed cascade signal amplification for precise phenotypic enumeration of CTCs

Mikrochim Acta. 2024 Nov 12;191(12):736. doi: 10.1007/s00604-024-06825-z.

Abstract

The inability of surgical biopsy to monitor the dynamic evolution of cancer cells hampers its capacity to reflect real-time tumor heterogeneity. Circulating tumor cells (CTCs), as a crucial target in liquid biopsy, offer a novel approach for accurate monitoring of tumors. However, the rarity and complex phenotype resulting from epithelial-mesenchymal transition pose challenges for conventional methods such as CellSearch and immunohistochemistry, which have insufficient ability for simultaneous phenotyping and enumeration of CTCs. The enumeration of a single phenotype CTCs is insufficient for accurately assessing disease progression. Herein, we propose a strategy to address this issue by fabricating an electrochemiluminescence cytosensor via the integration of dual-target enrichment and nanozymes-catalyzed cascade signal amplification. The graphene oxide@hollow mesoporous Prussian blue/Pt (GO@HMPB/Pt) complex, possessing a large specific surface area and exceptional catalytic activity, is employed for loading a substantial amount of luminol as the signal probe. Dual-target magnetic PPy@Fe3O4/Au-antibody/aptamer is utilized for the magnetic capture of both epithelial and interstitial CTCs. Glutathione (GSH) can disrupt the Au-S bond on aptamer by a thiol exchange reaction and selectively releases a specific subset of phenotypic CTCs, thereby facilitating the efficient capture, accurate classification, and ultrasensitive detection of CTCs in peripheral blood. Using the epithelial MCF-7 and mesenchymal Hela cells as models, the ECL cytosensor demonstrates excellent performance in identifying cells spiked into whole blood. This study presents a novel approach for early detection of metastasis, tracking tumor recurrence, and monitoring therapeutic efficacy.

Keywords: Circulating tumor cells; Dual-target magnetic separation; Electrochemiluminescence cytosensor; Nanozymes-catalyzed cascade amplification; Tumor heterogeneity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide* / chemistry
  • Biosensing Techniques* / methods
  • Catalysis
  • Electrochemical Techniques* / instrumentation
  • Electrochemical Techniques* / methods
  • Ferrocyanides* / chemistry
  • Glutathione / chemistry
  • Gold / chemistry
  • Graphite* / chemistry
  • Humans
  • Luminescent Measurements / methods
  • Luminol / chemistry
  • MCF-7 Cells
  • Magnetite Nanoparticles / chemistry
  • Neoplastic Cells, Circulating* / pathology
  • Platinum / chemistry

Substances

  • Graphite
  • Aptamers, Nucleotide
  • graphene oxide
  • Ferrocyanides
  • ferric ferrocyanide
  • Luminol
  • Platinum
  • Gold
  • Glutathione
  • Magnetite Nanoparticles