Certain types of cationic metal ions,such as Mn^(2+)are able to activate immune functions via the stimulator of interferon genes(STING)pathway,showing potential applications in eliciting antitumor immunity.How anionic...Certain types of cationic metal ions,such as Mn^(2+)are able to activate immune functions via the stimulator of interferon genes(STING)pathway,showing potential applications in eliciting antitumor immunity.How anionic ions interact with immune cells remains largely unknown.Herein,selecting from a range of cationic and anionic ions,we were excited to discover that MoO_(4)^(2-)could act as a cGAS-STING agonist and further confirmed the capability of Mn^(2+)to activate the cGAS-STING pathway.Inspired by such findings,we synthesized manganese molybdate nanoparticles with polyethylene glycol modification(MMP NDs)for cancer metalloimmunotherapy.Meanwhile,MMP NDs could consume glutathione(GSH)over-expressed in tumors and induce ferroptosis owing to high-valence Mo and Mn to elicit tumor-specific immune responses,which was further amplified by MMP-triggered the cGAS-STING activation.In turn,activated CD8+T cells to secrete high levels of interferonγ(IFN-γ)and reduced GPX4 expression in tumor cells to trigger ferroptosis-specific lipid peroxidation,which constituted a“cycle”of therapy.As a result,the metalloimmunotherapy with systemic administration of MMP NDs offered a remarkable tumor inhibition effect for a variety of tumor models.Our work for the first time discovered the ability of anionic metal ions to activate the immune system and rationally designed bimetallic oxide nanostructures as a multifunctional therapeutic nanoplatform for tumor immunotherapy.展开更多
基金supported by the National Research Programs of China(2022YFB3804604,2021YFF0701800)National Natural Science Foundation of China(U20A20254,52072253)+2 种基金Collaborative Innovation Center of Suzhou Nano Science and Technology,the 111 Project,Joint International Research Laboratory of Carbon-Based Functional Materials and Devices,a Jiangsu Natural Science Fund for Distinguished Young Scholars(BK20211544)Jiangsu Social Development Project(BE2019658)Suzhou Key Laboratory of Nanotechnology and Biomedicine.The authors also thank the website app.Biorender.com for the assistance in creating the Figures.
文摘Certain types of cationic metal ions,such as Mn^(2+)are able to activate immune functions via the stimulator of interferon genes(STING)pathway,showing potential applications in eliciting antitumor immunity.How anionic ions interact with immune cells remains largely unknown.Herein,selecting from a range of cationic and anionic ions,we were excited to discover that MoO_(4)^(2-)could act as a cGAS-STING agonist and further confirmed the capability of Mn^(2+)to activate the cGAS-STING pathway.Inspired by such findings,we synthesized manganese molybdate nanoparticles with polyethylene glycol modification(MMP NDs)for cancer metalloimmunotherapy.Meanwhile,MMP NDs could consume glutathione(GSH)over-expressed in tumors and induce ferroptosis owing to high-valence Mo and Mn to elicit tumor-specific immune responses,which was further amplified by MMP-triggered the cGAS-STING activation.In turn,activated CD8+T cells to secrete high levels of interferonγ(IFN-γ)and reduced GPX4 expression in tumor cells to trigger ferroptosis-specific lipid peroxidation,which constituted a“cycle”of therapy.As a result,the metalloimmunotherapy with systemic administration of MMP NDs offered a remarkable tumor inhibition effect for a variety of tumor models.Our work for the first time discovered the ability of anionic metal ions to activate the immune system and rationally designed bimetallic oxide nanostructures as a multifunctional therapeutic nanoplatform for tumor immunotherapy.
