Efficient ovalbumin delivery using a novel multifunctional micellar platform for targeted melanoma immunotherapy

Int J Pharm. 2019 Apr 5;560:1-10. doi: 10.1016/j.ijpharm.2019.01.027. Epub 2019 Jan 21.

Abstract

Cancer immunotherapy is considered to be one of the alternatives to traditional chemotherapy. It's known that foreign antigen, such as ovalbumin (OVA), can label tumor cells, leading to neoantigen recognition by cytotoxic T lymphocytes. Herein, a novel multifunctional micelle coated with PEGylated hyaluronic acid (HA) was prepared through self-assembly and electrostatic interaction. The OVA-loaded micelle with uniform size (132.1 ± 0.2 nm in diameter) exhibited favorable stability and sustained release profiles. The HA-coated micelle could target CD44-overexpressed cells and enhance the cellular uptake of OVA by 11.9 fold compared to free OVA. In vitro studies revealed that the cationic polymer, polyethyleneimine, could facilitate endosomal escape of OVA to label a tumor cell. After treatment with the OVA-loaded micelle, tumor growth in mice was significantly inhibited by 70% compared to the group treated with free OVA. All these results suggest the potential application of the immunotherapeutic micellar platform for melanoma treatment.

Keywords: Immunotherapy; Melanoma; Multifunctional micelle; Ovalbumin; Self-assembly.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antigens / immunology
  • Cell Line, Tumor
  • Delayed-Action Preparations
  • Drug Stability
  • Female
  • Hyaluronic Acid / chemistry*
  • Immunotherapy / methods*
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / immunology
  • Mice
  • Mice, Inbred C57BL
  • Micelles
  • Ovalbumin / administration & dosage*
  • Ovalbumin / immunology
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Polyethyleneimine / chemistry
  • Polymers / chemistry
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antigens
  • Delayed-Action Preparations
  • Micelles
  • Polymers
  • Polyethylene Glycols
  • Polyethyleneimine
  • Hyaluronic Acid
  • Ovalbumin