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Intracavitary Spraying of Nanoregulator-Encased Hydrogel Modulates Cholesterol Metabolism of Glioma-Supportive Macrophage for Postoperative Glioblastoma Immunotherapy.
Dong, Yuanmin; Zhang, Jing; Wang, Yan; Zhang, Yulin; Rappaport, Daniella; Yang, Zhenmei; Han, Maosen; Liu, Ying; Fu, Zhipeng; Zhao, Xiaotian; Tang, Chunwei; Shi, Chongdeng; Zhang, Daizhou; Li, Dawei; Ni, Shilei; Li, Anning; Cui, Jiwei; Li, Tao; Sun, Peng; Benny, Ofra; Zhang, Cai; Zhao, Kun; Chen, Chen; Jiang, Xinyi.
Afiliación
  • Dong Y; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong Province
  • Zhang J; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong Province
  • Wang Y; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong Province
  • Zhang Y; Department of Neurosurgery, Qilu Hospital and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Jinan, Shandong Province, 250012, China.
  • Rappaport D; Harry W. and Charlotte Ullman Labov Chair in Cancer Studies, Fraunhofer Innovation Platform (FIP_DD@HUJI), Institute for Drug Research, The School of Pharmacy, Faculty of Medicine | Ein Karem Campus, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel.
  • Yang Z; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong Province
  • Han M; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong Province
  • Liu Y; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong Province
  • Fu Z; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong Province
  • Zhao X; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong Province
  • Tang C; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong Province
  • Shi C; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong Province
  • Zhang D; Shandong Academy of Pharmaceutical Sciences, Jinan, Shandong Province, 250012, China.
  • Li D; Shandong Academy of Pharmaceutical Sciences, Jinan, Shandong Province, 250012, China.
  • Ni S; Department of Neurosurgery, Qilu Hospital and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Jinan, Shandong Province, 250012, China.
  • Li A; Department of Radiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Jinan, Shandong Province, 250012, China.
  • Cui J; Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong, 250100, China.
  • Li T; Department of General Surgery, Qilu Hospital, Shandong University, 44 Cultural West Road, Jinan, Shandong Province, 250012, China.
  • Sun P; Shandong University of Traditional Chinese Medicine, University Road, Jinan, Shandong Province, 250355, China.
  • Benny O; Harry W. and Charlotte Ullman Labov Chair in Cancer Studies, Fraunhofer Innovation Platform (FIP_DD@HUJI), Institute for Drug Research, The School of Pharmacy, Faculty of Medicine | Ein Karem Campus, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel.
  • Zhang C; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong Province
  • Zhao K; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong Province
  • Chen C; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong Province
  • Jiang X; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, Shandong Province
Adv Mater ; 36(13): e2311109, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38127403
ABSTRACT
Glioblastoma multiforme (GBM) is notoriously resistant to immunotherapy due to its intricate immunosuppressive tumor microenvironment (TME). Dysregulated cholesterol metabolism is implicated in the TME and promotes tumor progression. Here, it is found that cholesterol levels in GBM tissues are abnormally high, and glioma-supportive macrophages (GSMs), an essential "cholesterol factory", demonstrate aberrantly hyperactive cholesterol metabolism and efflux, providing cholesterol to fuel GBM growth and induce CD8+ T cells exhaustion. Bioinformatics analysis confirms that high 7-dehydrocholesterol reductase (DHCR7) level in GBM tissues associates with increased cholesterol biosynthesis, suppressed tumoricidal immune response, and poor patient survival, and DHCR7 expression level is significantly elevated in GSMs. Therefore, an intracavitary sprayable nanoregulator (NR)-encased hydrogel system to modulate cholesterol metabolism of GSMs is reported. The degradable NR-mediated ablation of DHCR7 in GSMs effectively suppresses cholesterol supply and activates T-cell immunity. Moreover, the combination of Toll-like receptor 7/8 (TLR7/8) agonists significantly promotes GSM polarization to antitumor phenotypes and ameliorates the TME. Treatment with the hybrid system exhibits superior antitumor effects in the orthotopic GBM model and postsurgical recurrence model. Altogether, the findings unravel the role of GSMs DHCR7/cholesterol signaling in the regulation of TME, presenting a potential treatment strategy that warrants further clinical trials.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Glioblastoma / Disacáridos / Glioma / Glucuronatos Límite: Humans Idioma: En Revista: Adv Mater Asunto de la revista: BIOFISICA / QUIMICA Año: 2024 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Glioblastoma / Disacáridos / Glioma / Glucuronatos Límite: Humans Idioma: En Revista: Adv Mater Asunto de la revista: BIOFISICA / QUIMICA Año: 2024 Tipo del documento: Article Pais de publicación: Alemania