A Self-Delivery Chimeric Peptide for Photodynamic Therapy Amplified Immunotherapy

Macromol Biosci. 2019 Apr;19(4):e1800410. doi: 10.1002/mabi.201800410. Epub 2018 Dec 21.

Abstract

In this paper, a self-delivery chimeric peptide PpIX-PEG8 -KVPRNQDWL is designed for photodynamic therapy (PDT) amplified immunotherapy against malignant melanoma. After self-assembly into nanoparticles (designated as PPMA), this self-delivery system shows high drug loading rate, good dispersion, and stability as well as an excellent capability in producing reactive oxygen species (ROS). After cellular uptake, the ROS generated under light irradiation could induce the apoptosis and/or necrosis of tumor cells, which would subsequently stimulate the anti-tumor immune response. On the other hand, the melanoma specific antigen (KVPRNQDWL) peptide could also activate the specific cytotoxic T cells for anti-tumor immunity. Compared to immunotherapy alone, the combined photodynamic immunotherapy exhibits significantly enhanced inhibition of melanoma growth. Both in vitro and in vivo investigations confirm that PDT of PPMA has a positive effect on anti-tumor immune response. This self-delivery system demonstrates a great potential of this PDT amplified immunotherapy strategy for advanced or metastatic tumor treatment.

Keywords: immunotherapy; melanoma; nano-vaccine; photodynamic therapy; self-delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / pharmacology*
  • COS Cells
  • Chlorocebus aethiops
  • Drug Delivery Systems*
  • Immunity, Cellular / drug effects
  • Immunotherapy*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy*
  • Mice
  • Peptides / pharmacology*
  • Photochemotherapy*
  • Reactive Oxygen Species / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology

Substances

  • Antigens, Neoplasm
  • Peptides
  • Reactive Oxygen Species