Programmed death-ligand 1 monoclonal antibody-linked immunoliposomes for synergistic efficacy of miR-130a and oxaliplatin in gastric cancers

Nanomedicine (Lond). 2019 Jul;14(13):1729-1744. doi: 10.2217/nnm-2019-0073. Epub 2019 Jul 10.

Abstract

Aim: PD-L1 monoclonal antibody-conjugated miR-130a/oxaliplatin-loaded immunoliposomes were constructed for enhanced therapeutic efficacy against gastric cancer. Materials & methods: The in vitro antitumor efficacy of the immunoliposomes was evaluated by cell viability, cell invasion, cell apoptosis and western blot analysis and in vivo antitumor efficacy was evaluated in a HGC27-bearing tumor xenograft model. Results: The inhibitory role of miR-130a was demonstrated in HGC27 cells by the downregulation of RAB5A and FOCL1 signaling pathways. Consequently, PD-miOXNP exhibited the strongest anticancer activity in vitro compared with any other formulation. PD-miOXNP showed a significantly higher anticancer efficacy in HGC27 tumors with reduced Ki67+ cells and increased TUNEL+ cells for mice group. Conclusion: PD-L1 monoclonal antibody-conjugated immunoliposomes have immense potential to be applied as a next-generation nanomedicine for PD-L1-positive gastric cancers.

Keywords: PD-L1; gastric cancers; immunoliposome; miRNA-130a; oxaliplatin; targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • B7-H1 Antigen* / antagonists & inhibitors
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunoconjugates / chemistry
  • Liposomes / chemistry
  • Mice, Inbred BALB C
  • MicroRNAs / administration & dosage*
  • MicroRNAs / therapeutic use
  • Oxaliplatin / administration & dosage*
  • Oxaliplatin / therapeutic use
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • B7-H1 Antigen
  • Immunoconjugates
  • Liposomes
  • MIRN130 microRNA, human
  • MicroRNAs
  • Oxaliplatin