A Trojan-Horse-Like Biomimetic Nano-NK to Elicit an Immunostimulatory Tumor Microenvironment for Enhanced GBM Chemo-Immunotherapy
Long Zhang
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, 221004 China
Search for more papers by this authorYining Zhang
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, 221004 China
Search for more papers by this authorXu Wang
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, 221004 China
Search for more papers by this authorYi Zhou
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, 221004 China
Search for more papers by this authorJi Qi
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, 221004 China
Search for more papers by this authorLinbo Gu
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, 221004 China
Search for more papers by this authorQiu Zhao
Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, Anhui, 230001 China
Search for more papers by this authorCorresponding Author
Rutong Yu
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Xiuping Zhou
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorLong Zhang
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, 221004 China
Search for more papers by this authorYining Zhang
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, 221004 China
Search for more papers by this authorXu Wang
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, 221004 China
Search for more papers by this authorYi Zhou
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, 221004 China
Search for more papers by this authorJi Qi
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, 221004 China
Search for more papers by this authorLinbo Gu
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, 221004 China
Search for more papers by this authorQiu Zhao
Department of Anesthesiology, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, Anhui, 230001 China
Search for more papers by this authorCorresponding Author
Rutong Yu
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Xiuping Zhou
Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, 221002 China
Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 2210002 China
E-mail: [email protected]; [email protected]
Search for more papers by this authorAbstract
Although the chemo- and immuno-therapies have obtained good responses for several solid tumors, including those with brain metastasis, their clinical efficacy in glioblastoma (GBM) is disappointing. The lack of safe and effective delivery systems across the blood-brain barrier (BBB) and the immunosuppressive tumor microenvironment (TME) are two main hurdles for GBM therapy. Herein, a Trojan-horse-like nanoparticle system is designed, which encapsulates biocompatible PLGA-coated temozolomide (TMZ) and IL-15 nanoparticles (NPs) with cRGD-decorated NK cell membrane (R-NKm@NP), to elicit the immunostimulatory TME for GBM chemo-immunotherapy. Taking advantage of the outer NK cell membrane cooperating with cRGD, the R-NKm@NPs effectively traversed across the BBB and targeted GBM. In addition, the R-NKm@NPs exhibited good antitumor ability and prolonged the median survival of GBM-bearing mice. Notably, after R-NKm@NPs treatment, the locally released TMZ and IL-15 synergistically stimulated the proliferation and activation of NK cells, leading to the maturation of dendritic cells and infiltration of CD8+ cytotoxic T cells, eliciting an immunostimulatory TME. Lastly, the R-NKm@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- and immuno-therapies in the future.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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