Glutathione-depletion mesoporous organosilica nanoparticles as a self-adjuvant and Co-delivery platform for enhanced cancer immunotherapy.

Abstract

Silica based nanoparticles have emerged as a promising vaccine delivery system for cancer immunotherapy, but their bio-degradability, adjuvanticity and the resultant antitumor activity remain to be largely improved. In this study, we report biodegradable glutathione-depletion dendritic mesoporous organosilica nanoparticles (GDMON) with a tetrasulfide-incorporated framework as a novel co-delivery platform in cancer immunotherapy. Functionalized GDMON are capable of co-delivering an antigen protein (ovalbumin) and a toll-like receptor 9 (TLR9) agonist into antigen presenting cells (APCs) and inducing endosome escape. Moreover, decreasing the intracellular glutathione (GSH) level through the -S-S-/GSH redox chemistry increases the ROS generation level both in vitro and in vivo, facilitating cytotoxic T lymphocyte (CTL) proliferation and reducing tumour growth in an aggressive B16-OVA melanoma tumour model. Our results have shown the potential of GDMON as a novel self-adjuvant and co-delivery nanocarrier for cancer vaccine.

• Authors: Yao Lu, Yannan Yang, Zhengying Gu, Jun Zhang, Hao Song, Guangya Xiang, Chengzhong Yu
• Journal: Biomaterials (Biomaterials) Vol. 175 Pg. 82-92 (08 2018) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 29803106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Cancer Vaccines
• Oligodeoxyribonucleotides
• Toll-Like Receptor 9
• Silicon Dioxide
• Polyethyleneimine
• Ovalbumin
• Glutathione

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Antigen-Presenting Cells (metabolism)
• Cancer Vaccines (administration & dosage)
• Cell Line, Tumor
• Cell Proliferation
• Endosomes (physiology)
• Glutathione (metabolism)
• Humans
• Immunotherapy
• Melanoma, Experimental (immunology, pathology, therapy)
• Mice
• Nanoparticles (chemistry)
• Oligodeoxyribonucleotides (administration & dosage)
• Ovalbumin (administration & dosage)
• Oxidation-Reduction
• Polyethyleneimine (chemistry)
• Porosity
• Silicon Dioxide (chemistry)
• T-Lymphocytes, Cytotoxic (pathology)
• Toll-Like Receptor 9 (agonists)