Intracavitary Spraying of Nanoregulator-Encased Hydrogel Modulates Cholesterol Metabolism of Glioma-Supportive Macrophage for Postoperative Glioblastoma Immunotherapy

Intracavitary Spraying of Nanoregulator-Encased Hydrogel Modulates Cholesterol Metabolism of Glioma-Supportive Macrophage for Postoperative Glioblastoma Immunotherapy

© 2023 Wiley‐VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 13 vom: 21. März, Seite e2311109
1. Verfasser: Dong, Yuanmin (VerfasserIn)
Weitere Verfasser: 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
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article CD8+ T cells exhaustion TLR7/8 agonists cholesterol metabolism glioma‐supportive macrophage polarization sprayable hydrogel Hydrogels O-(glucuronic acid 2-sulfate)-(1--4)-O-(2,5)-anhydromannitol 6-sulfate 98632-68-9 Cholesterol mehr... 97C5T2UQ7J Disaccharides Glucuronates
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100 1 |a Dong, Yuanmin  |e verfasserin  |4 aut 
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520 |a 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 
650 4 |a Journal Article 
650 4 |a CD8+ T cells exhaustion 
650 4 |a TLR7/8 agonists 
650 4 |a cholesterol metabolism 
650 4 |a glioma‐supportive macrophage polarization 
650 4 |a sprayable hydrogel 
650 7 |a Hydrogels  |2 NLM 
650 7 |a O-(glucuronic acid 2-sulfate)-(1--4)-O-(2,5)-anhydromannitol 6-sulfate  |2 NLM 
650 7 |a 98632-68-9  |2 NLM 
650 7 |a Cholesterol  |2 NLM 
650 7 |a 97C5T2UQ7J  |2 NLM 
650 7 |a Disaccharides  |2 NLM 
650 7 |a Glucuronates  |2 NLM 
700 1 |a Zhang, Jing  |e verfasserin  |4 aut 
700 1 |a Wang, Yan  |e verfasserin  |4 aut 
700 1 |a Zhang, Yulin  |e verfasserin  |4 aut 
700 1 |a Rappaport, Daniella  |e verfasserin  |4 aut 
700 1 |a Yang, Zhenmei  |e verfasserin  |4 aut 
700 1 |a Han, Maosen  |e verfasserin  |4 aut 
700 1 |a Liu, Ying  |e verfasserin  |4 aut 
700 1 |a Fu, Zhipeng  |e verfasserin  |4 aut 
700 1 |a Zhao, Xiaotian  |e verfasserin  |4 aut 
700 1 |a Tang, Chunwei  |e verfasserin  |4 aut 
700 1 |a Shi, Chongdeng  |e verfasserin  |4 aut 
700 1 |a Zhang, Daizhou  |e verfasserin  |4 aut 
700 1 |a Li, Dawei  |e verfasserin  |4 aut 
700 1 |a Ni, Shilei  |e verfasserin  |4 aut 
700 1 |a Li, Anning  |e verfasserin  |4 aut 
700 1 |a Cui, Jiwei  |e verfasserin  |4 aut 
700 1 |a Li, Tao  |e verfasserin  |4 aut 
700 1 |a Sun, Peng  |e verfasserin  |4 aut 
700 1 |a Benny, Ofra  |e verfasserin  |4 aut 
700 1 |a Zhang, Cai  |e verfasserin  |4 aut 
700 1 |a Zhao, Kun  |e verfasserin  |4 aut 
700 1 |a Chen, Chen  |e verfasserin  |4 aut 
700 1 |a Jiang, Xinyi  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Advanced materials (Deerfield Beach, Fla.)  |d 1998  |g 36(2024), 13 vom: 21. März, Seite e2311109  |w (DE-627)NLM098206397  |x 1521-4095  |7 nnas 
773 1 8 |g volume:36  |g year:2024  |g number:13  |g day:21  |g month:03  |g pages:e2311109 
856 4 0 |u http://dx.doi.org/10.1002/adma.202311109  |3 Volltext 
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