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The lack of safe and effective delivery systems across the blood\u2010brain barrier (BBB) and the immunosuppressive tumor microenvironment (TME) are two main hurdles for GBM therapy. Herein, a Trojan\u2010horse\u2010like nanoparticle system is designed, which encapsulates biocompatible PLGA\u2010coated temozolomide (TMZ) and IL\u201015 nanoparticles (NPs) with cRGD\u2010decorated NK cell membrane (R\u2010NKm@NP), to elicit the immunostimulatory TME for GBM chemo\u2010immunotherapy. Taking advantage of the outer NK cell membrane cooperating with cRGD, the R\u2010NKm@NPs effectively traversed across the BBB and targeted GBM. In addition, the R\u2010NKm@NPs exhibited good antitumor ability and prolonged the median survival of GBM\u2010bearing mice. Notably, after R\u2010NKm@NPs treatment, the locally released TMZ and IL\u201015 synergistically stimulated the proliferation and activation of NK cells, leading to the maturation of dendritic cells and infiltration of CD8<jats:sup>+<\/jats:sup> cytotoxic T cells, eliciting an immunostimulatory TME. Lastly, the R\u2010NKm@NPs not only effectively prolonged the metabolic cycling time of the drugs in vivo, but also has no noticeable side effects. This study may offer valuable insights for developing biomimetic nanoparticles to potentiate GBM chemo\u2010 and immuno\u2010therapies in the future.<\/jats:p>","DOI":"10.1002\/smll.202301439","type":"journal-article","created":{"date-parts":[[2023,7,8]],"date-time":"2023-07-08T03:45:34Z","timestamp":1688787934000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["A Trojan\u2010Horse\u2010Like Biomimetic Nano\u2010NK to Elicit an Immunostimulatory Tumor Microenvironment for Enhanced GBM Chemo\u2010Immunotherapy"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6811-0439","authenticated-orcid":false,"given":"Long","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Nervous System Diseases Xuzhou Medical University  Xuzhou Jiangsu 221002 China"},{"name":"Department of Neurosurgery the Affiliated Hospital of Xuzhou Medical University  Xuzhou Jiangsu 2210002 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