With an intensive understanding of the mechanism of immune system,developing a therapeutic tumor vaccine is one of the most perspective strategy of cancer immunotherapy.In this study,we report a facile approach to pre...With an intensive understanding of the mechanism of immune system,developing a therapeutic tumor vaccine is one of the most perspective strategy of cancer immunotherapy.In this study,we report a facile approach to prepare graphene oxide(GO)-based therapeutic cancer-nanovaccine.The model antigen(ovalbumin,OVA)and adjuvant(CpG ODN),are conjugated with GO-PEI nanosheet through electrostatic interaction.The addition of PEG can improve biocompatibility and prevent nanoparticle aggregation.The prepared GO-based nanovaccine,GO-PEI-OVA-PEG-CpG,exhibits good biocompatibility and low toxicity both in vivo and in vitro.More importantly,it can efficiently induce the maturation of dendritic cells(DCs),the enhancement of antigen cross-presentation ability,and the amplification of cytokine production of immune cells.Impressively,this nanovaccine shows a remarkable therapeutic effect against preestablished B16-OVA-melanoma tumors,which can significantly inhibit tumor growth and prolong the survival time of the OVA-expressed tumor-bearing mice.Moreover,combining GO-PEI-OVA-PEG-CpG with NLG919,an IDO-1(indoleamine-2,3-dioxygenase)inhibitor which can regulate the tumor microenvironment,displays a synergistic therapeutic effect.These findings indicate the GO-PEI-OVA-PEG-CpG nanovaccine actively induces an antigen-specific antitumor immune response and it combined with NLG919 could achieve better therapeutic outcomes.展开更多
基金the financial support from Basic and Applied Basic Research Program of Hainan Province(Nos.2019RC209and 820RC646)the National Natural Science Foundation of China(No.81860037)China Postdoctoral Science Special Foundations(Nos.2015T80488 and 2014T70459)。
文摘With an intensive understanding of the mechanism of immune system,developing a therapeutic tumor vaccine is one of the most perspective strategy of cancer immunotherapy.In this study,we report a facile approach to prepare graphene oxide(GO)-based therapeutic cancer-nanovaccine.The model antigen(ovalbumin,OVA)and adjuvant(CpG ODN),are conjugated with GO-PEI nanosheet through electrostatic interaction.The addition of PEG can improve biocompatibility and prevent nanoparticle aggregation.The prepared GO-based nanovaccine,GO-PEI-OVA-PEG-CpG,exhibits good biocompatibility and low toxicity both in vivo and in vitro.More importantly,it can efficiently induce the maturation of dendritic cells(DCs),the enhancement of antigen cross-presentation ability,and the amplification of cytokine production of immune cells.Impressively,this nanovaccine shows a remarkable therapeutic effect against preestablished B16-OVA-melanoma tumors,which can significantly inhibit tumor growth and prolong the survival time of the OVA-expressed tumor-bearing mice.Moreover,combining GO-PEI-OVA-PEG-CpG with NLG919,an IDO-1(indoleamine-2,3-dioxygenase)inhibitor which can regulate the tumor microenvironment,displays a synergistic therapeutic effect.These findings indicate the GO-PEI-OVA-PEG-CpG nanovaccine actively induces an antigen-specific antitumor immune response and it combined with NLG919 could achieve better therapeutic outcomes.
