Yeast β-D-glucan functionalized graphene oxide for macrophage-targeted delivery of CpG oligodeoxynucleotides and synergistically enhanced antitumor immunity

Abstract

Immunostimulatory CpG oligodeoxynucleotides (CpG ODNs) show strong potential in cancer immunotherapy. However, therapeutic efficacy of CpG ODNs is hindered due to rapid nuclease degradation and insufficient cellular uptake. Transfecting CpG ODNs into antigen presenting cells (APCs) is vital to enhance their therapeutic efficacy while reduce the potential side effects. Herein, a multifunctional CpG ODNs vector was fabricated through functionalization of graphene oxide (GO) with yeast β-D-glucan, and its potential in cancer immunotherapy was further investigated. GO-β-D-glucan protected CpG ODNs from nuclease digestion. β-D-glucan endowed the delivery system with targeting ability for macrophage due to its recognition with dectin-1. Thus, GO-β-D-glucan enhanced the delivery of CpG ODNs into RAW264.7 cells due to dectin-1-mediated endocytosis. More importantly, β-D-glucan functioned synergistically with CpG ODNs in inducing antitumor immunity. GO-β-D-glucan/CpG ODNs inhibited the tumor cells growth more effectively. This work provides a macrophage-targeted CpG ODNs delivery system for cancer immunotherapy.Graphic abstract.