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targeted delivery of a STING agonist to brain tumors using bioengineered protein nanoparticles for enhanced immunotherapy

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Bioactive Materials 2022年第10期7卷 232-248页

作者： Bin Wang Maoping Tang Ziwei Yuan Zhongyu Li Bin Hu Xin Bai Jinxian Chu Xiaoyang Xu Xue-Qing Zhang Engineering Research Center of Cell&Therapeutic Antibody Ministry of EducationSchool of PharmacyShanghai Jiao Tong University800 Dongchuan RoadShanghai200240PR China Department of Chemical and Materials Engineering New Jersey Institute of TechnologyNewarkNJ07102USA

immunotherapy is emerging as a powerful tool for combating many human ***,the application of this life-saving treatment in serious brain diseases,including glioma,is greatly *** major obstacle is the lack of effective technologies for transporting therapeutic agents across the blood-brain barrier(BBB)and achieving targeted delivery to specific cells once across the ***,an iron storage protein,traverses the BBB via receptor-mediated transcytosis by binding to transferrin receptor 1(TfR1)overexpressed on BBB endothelial ***,we developed bioengineered ferritin nanoparticles as drug delivery carriers that enable the targeted delivery of a small-molecule immunomodulator to achieve enhanced immunotherapeutic efficacy in an orthotopic glioma-bearing mouse *** fused different glioma-targeting moieties on self-assembled ferritin nanoparticles via genetic engineering,and RGE fusion protein nanoparticles(RGE-HFn NPs)were identified as the best ***,RGE-HFn NPs encapsulating a stimulator of interferon genes(STING)agonist(SR717@RGE-HFn NPs)maintained stable self-assembled structure and targeting properties even after traversing the *** the glioma-bearing mouse model,SR717@RGE-HFn NPs elicited a potent local innate immune response in the tumor microenvironment,resulting in significant tumor growth inhibition and prolonged ***,this biomimetic brain delivery platform offers new opportunities to overcome the BBB and provides a promising approach for brain drug delivery and immunotherapy in patients with glioma.

关键词： Blood brain barrier Bioengineered protein nanoparticles Dual-targeting property STING agonist glioma-targeted immunotherapy

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