Immunotherapy of Hepatocellular Carcinoma with Magnetic PD-1 Peptide-Imprinted Polymer Nanocomposite and Natural Killer Cells

Biomolecules. 2019 Oct 25;9(11):651. doi: 10.3390/biom9110651.

Abstract

Programmed cell death protein 1 (PD-1) is a biomarker on the surface of cells with a role in promoting self-tolerance by suppressing the inflammatory activity of T cells. In this work, one peptide of PD-1 was used as the template for molecular imprinting to form magnetic peptide-imprinted poly(ethylene-co-vinyl alcohol) composite nanoparticles (MPIP NPs). The nanoparticles were characterized by dynamic light scattering (DLS), high-performance liquid chromatography (HPLC), Brunauer-Emmett-Teller (BET) analysis, and superconducting quantum interference device (SQUID) analysis. Natural killer 92 (NK-92) cells were added to these composite nanoparticles and then incubated with human hepatoma (HepG2) cells. The viability and the apoptosis pathway of HepG2 were then studied using cell counting kit-8 (CCK8) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. These nanoparticles were found to significantly enhance the activity of natural killer cells toward HepG2 cells by increasing the expression of nuclear factor kappa B (NF-κB), caspase 8, and especially caspase 3.

Keywords: human hepatoma cells; immunotherapy; magnetic nanoparticles; natural killer cells; peptide-imprinted polymer; programmed cell death protein 1 (PD-1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line
  • Cell Survival / drug effects
  • Gene Expression / drug effects
  • Humans
  • Immunotherapy
  • Iron Compounds / administration & dosage*
  • Killer Cells, Natural / immunology*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / immunology
  • Liver Neoplasms / therapy*
  • Magnetic Phenomena
  • Molecular Imprinting
  • Nanocomposites / administration & dosage*
  • Peptides / administration & dosage*
  • Polyvinyls / administration & dosage*
  • Programmed Cell Death 1 Receptor / administration & dosage*

Substances

  • Iron Compounds
  • Pdcd1 protein, mouse
  • Peptides
  • Polyvinyls
  • Programmed Cell Death 1 Receptor
  • ethylene-vinyl alcohol copolymer