Development of a DNA Aptamer against Multidrug-Resistant Hepatocellular Carcinoma for In Vivo Imaging

ACS Appl Mater Interfaces. 2021 Nov 24;13(46):54656-54664. doi: 10.1021/acsami.1c12391. Epub 2021 Nov 15.

Abstract

Hepatocellular carcinoma (HCC) is a type of cancer that has high rates of recurrence and mortality. One of the most important factors that lead to treatment failure of HCC is the acquisition of multidrug resistance (MDR). Development of specific ligands for multidrug-resistant HCC will provide useful molecular tools for precise diagnosis and targeted theranostics. Herein, a multidrug-resistant HCC cell (HepG2/MDR)-specific aptamer was developed through Cell-SELEX (systematic evolution of ligands by exponential enrichment) technology. With dissociation constants lying in the nanomolar range, the molecularly designed PS-ZL-7c aptamer showed great selectivity to drug-resistant cancer cells. The in vivo imaging results illustrated that the PS-ZL-7c specifically accumulated in the drug-resistant tumors but not in drug-sensitive tumors and normal tissues, indicating that the PS-ZL-7c aptamer possessed excellent potential as a targeting ligand for precise diagnosis and target theranostics of multidrug-resistant HCC.

Keywords: Cell-SELEX; aptamer; hepatocellular carcinoma; in vivo imaging; multidrug resistance.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Aptamers, Nucleotide / chemical synthesis
  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / pharmacology*
  • Carcinoma, Hepatocellular / diagnostic imaging
  • Carcinoma, Hepatocellular / drug therapy*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Development*
  • Drug Resistance, Neoplasm / drug effects
  • Drug Screening Assays, Antitumor
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Optical Imaging*
  • SELEX Aptamer Technique*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Aptamers, Nucleotide