Exploration and functionalization of M1-macrophage extracellular vesicles for effective accumulation in glioblastoma and strong synergistic therapeutic effects
文献类型：期刊论文
| 作者 | Wang, Xiaojun1,2,3; Ding, Hui4,5; Li, Zongyang1; Peng, Yaonan6; Tan, Hui1; Wang, Changlong2,7; Huang, Guodong1; Li, Weiping1; Ma, Guanghui2,7; Wei, Wei2,7 |
| 刊名 | SIGNAL TRANSDUCTION AND TARGETED THERAPY
 |
| 出版日期 | 2022-03-16 |
| 卷号 | 7期号:1页码:16 |
| ISSN号 | 2095-9907 |
| DOI | 10.1038/s41392-022-00894-3 |
| 英文摘要 | Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with an extremely low survival rate. New and effective approaches for treatment are therefore urgently needed. Here, we successfully developed M1-like macrophage-derived extracellular vesicles (M1EVs) that overcome multiple challenges via guidance from two macrophage-related observations in clinical specimens from GBM patients: enrichment of M2 macrophages in GBM; and origination of a majority of infiltrating macrophage from peripheral blood. To maximize the synergistic effect, we further functionalized the membranes of M1EVs with two hydrophobic agents (the chemical excitation source CPPO (C) and the photosensitizer Ce6 (C)) and loaded the hydrophilic hypoxia-activated prodrug AQ4N (A) into the inner core of the M1EVs. After intravenous injection, the inherent nature of M1-derived extracellular vesicles CCA-M1EVs allowed for blood-brain barrier penetration, and modulated the immunosuppressive tumor microenvironment via M2-to-M1 polarization, which increased hydrogen peroxide (H2O2) levels. Furthermore, the reaction between H2O2 and CPPO produced chemical energy, which could be used for Ce6 activation to generate large amounts of reactive oxygen species to achieve chemiexcited photodynamic therapy (CDT). As this reaction consumed oxygen, the aggravation of tumor hypoxia also led to the conversion of non-toxic AQ4N into toxic AQ4 for chemotherapy. Therefore, CCA-M1EVs achieved synergistic immunomodulation, CDT, and hypoxia-activated chemotherapy in GBM to exert a potent therapeutic effect. Finally, we demonstrated the excellent effect of CCA-M1EVs against GBM in cell-derived xenograft and patient-derived xenograft models, underscoring the strong potential of our highly flexible M1EVs system to support multi-modal therapies for difficult-to-treat GBM. |
| WOS关键词 | BRAIN ; EXOSOMES ; DELIVERY ; COMMUNICATION ; CELLS |
| 资助项目 | National Natural Science Foundation of China[82003303] ; National Natural Science Foundation of China[82102205] ; National Natural Science Foundation of China[81772685] ; National Natural Science Foundation of China[21821005] ; National Natural Science Foundation of China[U2001224] ; National Key R&D Program of China[2017YFA0207900] ; National Key Research and Development Program of China[2020YFC1316900] ; National Key Research and Development Program of China[2020YFC1316901] ; Science and Technology Innovation Committee of Shenzhen Municipality[ZDSYS20140509173142601] ; Science and Technology Innovation Committee of Shenzhen Municipality[ZDSYS201707281114196] ; Science and Technology Innovation Committee of Shenzhen Municipality[ZDSYS20200811142600003] ; Science and Technology Innovation Committee of Shenzhen Municipality[JSGG20191129144225464] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000769458900001 |
| 出版者 | SPRINGERNATURE |
| 资助机构 | National Natural Science Foundation of China ; National Key R&D Program of China ; National Key Research and Development Program of China ; Science and Technology Innovation Committee of Shenzhen Municipality |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/52362]  |
| 专题 | 中国科学院过程工程研究所 |
| 通讯作者 | Li, Weiping; Ma, Guanghui; Wei, Wei |
| 作者单位 | 1.Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Shenzhen Key Lab Neurosurg,Dept Neurosurg, Shenzhen 518035, Guangdong, Peoples R China 2.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China 3.Capital Med Univ, Beijing Chaoyang Hosp, Dept Ophthalmol, Beijing 100020, Peoples R China 4.Shenzhen Univ, Hlth Sci Ctr, Affiliated Hosp 1, Shenzhen Peoples Hosp 2,Dept Otolaryngol, Shenzhen 518110, Guangdong, Peoples R China 5.Shenzhen Univ, Hlth Sci Ctr, Affiliated Hosp 1, Shenzhen Peoples Hosp 2,Inst Translat Med, Shenzhen 518110, Guangdong, Peoples R China 6.Jinling Hosp, Dept Neurosurg, Nanjing 210000, Jiangsu, Peoples R China 7.Univ Chinese Acad Sci, Sch Chem Engn, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Xiaojun,Ding, Hui,Li, Zongyang,et al. Exploration and functionalization of M1-macrophage extracellular vesicles for effective accumulation in glioblastoma and strong synergistic therapeutic effects[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2022,7(1):16. |
| APA | Wang, Xiaojun.,Ding, Hui.,Li, Zongyang.,Peng, Yaonan.,Tan, Hui.,...&Wei, Wei.(2022).Exploration and functionalization of M1-macrophage extracellular vesicles for effective accumulation in glioblastoma and strong synergistic therapeutic effects.SIGNAL TRANSDUCTION AND TARGETED THERAPY,7(1),16. |
| MLA | Wang, Xiaojun,et al."Exploration and functionalization of M1-macrophage extracellular vesicles for effective accumulation in glioblastoma and strong synergistic therapeutic effects".SIGNAL TRANSDUCTION AND TARGETED THERAPY 7.1(2022):16. |
入库方式： OAI收割
来源：过程工程研究所
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