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A Virus‐Mimicking Nucleic Acid Nanogel Reprograms Microglia and Macrophages for Glioblastoma Therapy
Author(s) -
Gao Xihui,
Li Sha,
Ding Fei,
Liu Xinlong,
Wu Yijing,
Li Jing,
Feng Jing,
Zhu Xinyuan,
Zhang Chuan
Publication year - 2021
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.202006116
Subject(s) - nanogel , microglia , tumor microenvironment , immune system , nucleic acid , cancer research , immunotherapy , in vivo , u87 , macrophage , biology , materials science , glioma , in vitro , immunology , drug delivery , inflammation , nanotechnology , biochemistry , microbiology and biotechnology
Immunotherapy is recognized as one of the most promising approaches to treat cancers. However, its effect in glioblastoma (GBM) treatment is insufficient, which can in part be attributed to the immunosuppressive tumor microenvironment (TME). Microglia and macrophages are the main immune infiltrating cells in the TME of GBM. Unfortunately, instead of initiating the anti‐tumor response, GBM‐infiltrating microglia and macrophages switch to a tumor‐promoting phenotype (M2), and support tumor growth, angiogenesis, and immunosuppression by the release of cytokines. In this work, a virus‐mimicking membrane‐coated nucleic acid nanogel Vir‐Gel embedded with therapeutic miRNA is developed, which can reprogram microglia and macrophages from a pro‐invasive M2 phenotype to an anti‐tumor M1 phenotype. By mimicking the virus infection process, Vir‐Gel significantly enhances the targetability and cell uptake efficiency of the miR155‐bearing nucleic acid nanogel. In vivo evaluations demonstrate that Vir‐Gel apparently prolongs the circulation lifetime of miR155 and endows it with an active tumor‐targeting capability and excellent tumor inhibition efficacy. Owing to its noninvasive feature and effective delivery capability, the virus‐mimicking nucleic acid nanogel provides a general and convenient platform that can successfully treat a wide range of diseases.