Doxorubicin‐loaded nanoparticle coated with endothelial cells‐derived exosomes for immunogenic chemotherapy of glioblastoma
Abstract Treatments of glioblastoma (GBM) have not been very effective, largely due to the inefficiency of drugs in penetrating the blood brain barrier (BBB). In this study, we investigated the potential of exosome‐coated doxorubicin (DOX)‐loaded nanoparticles (ENPDOX) in BBB penetration, inducing i...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-09-01
|
| Series: | Bioengineering & Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/btm2.10203 |
| _version_ | 1818647232714375168 |
|---|---|
| author | Chao Zhang Jian Song Lei Lou Xuejiao Qi Lei Zhao Bo Fan Guozhu Sun Zhongqiang Lv Zhenzeng Fan Baohua Jiao Jiankai Yang |
| author_facet | Chao Zhang Jian Song Lei Lou Xuejiao Qi Lei Zhao Bo Fan Guozhu Sun Zhongqiang Lv Zhenzeng Fan Baohua Jiao Jiankai Yang |
| author_sort | Chao Zhang |
| collection | DOAJ |
| description | Abstract Treatments of glioblastoma (GBM) have not been very effective, largely due to the inefficiency of drugs in penetrating the blood brain barrier (BBB). In this study, we investigated the potential of exosome‐coated doxorubicin (DOX)‐loaded nanoparticles (ENPDOX) in BBB penetration, inducing immunogenic cell death (ICD) and promoting survival of GBM‐bearing mice. DOX‐loaded nanoparticles (NPDOX) were coated with exosomes prepared from mouse brain endothelial bEnd.3 cells. ENPDOX cellular uptake was examined. Penetration of ENPDOX through the BBB was tested in an in vitro transwell system and a GBM mouse model. The effects of ENPDOX in inducing apoptosis and ICD were assessed. Finally, the efficacy of ENPDOX in the treatment of GBM‐bearing mice was assessed. ENPDOX was taken up by bEnd.3 cells and could penetrate the BBB both in vitro and in vivo. In vitro, ENDDOX induced apoptosis and ICD of glioma GL261 cells. Systemic administration of ENPDOX resulted in maturation of dendritic cells, activation of cytotoxic cells, altered production of cytokines, suppressed proliferation and increased apoptosis of GBM cells in vivo and prolonged survival of GBM‐bearing mice. Our findings indicate that ENPDOX may be a potent therapeutic strategy for GBM which warrants further investigation in clinical application. |
| first_indexed | 2024-12-17T00:59:16Z |
| format | Article |
| id | doaj.art-7e934baf02b94fa1a4295f5ed2de0e4c |
| institution | Directory Open Access Journal |
| issn | 2380-6761 |
| language | English |
| last_indexed | 2024-12-17T00:59:16Z |
| publishDate | 2021-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj.art-7e934baf02b94fa1a4295f5ed2de0e4c2022-12-21T22:09:31ZengWileyBioengineering & Translational Medicine2380-67612021-09-0163n/an/a10.1002/btm2.10203Doxorubicin‐loaded nanoparticle coated with endothelial cells‐derived exosomes for immunogenic chemotherapy of glioblastomaChao Zhang0Jian Song1Lei Lou2Xuejiao Qi3Lei Zhao4Bo Fan5Guozhu Sun6Zhongqiang Lv7Zhenzeng Fan8Baohua Jiao9Jiankai Yang10Department of Neurosurgery, the Second Hospital of Hebei Medical University Shijiazhuang Hebei ChinaDepartment of Neurosurgery, the Second Hospital of Hebei Medical University Shijiazhuang Hebei ChinaDepartment of Neurosurgery, the Second Hospital of Hebei Medical University Shijiazhuang Hebei ChinaDepartment of Neurosurgery, the Second Hospital of Hebei Medical University Shijiazhuang Hebei ChinaDepartment of Neurosurgery, the Second Hospital of Hebei Medical University Shijiazhuang Hebei ChinaDepartment of Neurosurgery, the Second Hospital of Hebei Medical University Shijiazhuang Hebei ChinaDepartment of Neurosurgery, the Second Hospital of Hebei Medical University Shijiazhuang Hebei ChinaDepartment of Neurosurgery, the Second Hospital of Hebei Medical University Shijiazhuang Hebei ChinaDepartment of Neurosurgery, the Second Hospital of Hebei Medical University Shijiazhuang Hebei ChinaDepartment of Neurosurgery, the Second Hospital of Hebei Medical University Shijiazhuang Hebei ChinaDepartment of Neurosurgery, the Second Hospital of Hebei Medical University Shijiazhuang Hebei ChinaAbstract Treatments of glioblastoma (GBM) have not been very effective, largely due to the inefficiency of drugs in penetrating the blood brain barrier (BBB). In this study, we investigated the potential of exosome‐coated doxorubicin (DOX)‐loaded nanoparticles (ENPDOX) in BBB penetration, inducing immunogenic cell death (ICD) and promoting survival of GBM‐bearing mice. DOX‐loaded nanoparticles (NPDOX) were coated with exosomes prepared from mouse brain endothelial bEnd.3 cells. ENPDOX cellular uptake was examined. Penetration of ENPDOX through the BBB was tested in an in vitro transwell system and a GBM mouse model. The effects of ENPDOX in inducing apoptosis and ICD were assessed. Finally, the efficacy of ENPDOX in the treatment of GBM‐bearing mice was assessed. ENPDOX was taken up by bEnd.3 cells and could penetrate the BBB both in vitro and in vivo. In vitro, ENDDOX induced apoptosis and ICD of glioma GL261 cells. Systemic administration of ENPDOX resulted in maturation of dendritic cells, activation of cytotoxic cells, altered production of cytokines, suppressed proliferation and increased apoptosis of GBM cells in vivo and prolonged survival of GBM‐bearing mice. Our findings indicate that ENPDOX may be a potent therapeutic strategy for GBM which warrants further investigation in clinical application.https://doi.org/10.1002/btm2.10203blood brain barrierdoxorubicinexosome‐coated doxorubicin‐loaded nanoparticleglioblastomaimmunogenic cell death |
| spellingShingle | Chao Zhang Jian Song Lei Lou Xuejiao Qi Lei Zhao Bo Fan Guozhu Sun Zhongqiang Lv Zhenzeng Fan Baohua Jiao Jiankai Yang Doxorubicin‐loaded nanoparticle coated with endothelial cells‐derived exosomes for immunogenic chemotherapy of glioblastoma Bioengineering & Translational Medicine blood brain barrier doxorubicin exosome‐coated doxorubicin‐loaded nanoparticle glioblastoma immunogenic cell death |
| title | Doxorubicin‐loaded nanoparticle coated with endothelial cells‐derived exosomes for immunogenic chemotherapy of glioblastoma |
| title_full | Doxorubicin‐loaded nanoparticle coated with endothelial cells‐derived exosomes for immunogenic chemotherapy of glioblastoma |
| title_fullStr | Doxorubicin‐loaded nanoparticle coated with endothelial cells‐derived exosomes for immunogenic chemotherapy of glioblastoma |
| title_full_unstemmed | Doxorubicin‐loaded nanoparticle coated with endothelial cells‐derived exosomes for immunogenic chemotherapy of glioblastoma |
| title_short | Doxorubicin‐loaded nanoparticle coated with endothelial cells‐derived exosomes for immunogenic chemotherapy of glioblastoma |
| title_sort | doxorubicin loaded nanoparticle coated with endothelial cells derived exosomes for immunogenic chemotherapy of glioblastoma |
| topic | blood brain barrier doxorubicin exosome‐coated doxorubicin‐loaded nanoparticle glioblastoma immunogenic cell death |
| url | https://doi.org/10.1002/btm2.10203 |
| work_keys_str_mv | AT chaozhang doxorubicinloadednanoparticlecoatedwithendothelialcellsderivedexosomesforimmunogenicchemotherapyofglioblastoma AT jiansong doxorubicinloadednanoparticlecoatedwithendothelialcellsderivedexosomesforimmunogenicchemotherapyofglioblastoma AT leilou doxorubicinloadednanoparticlecoatedwithendothelialcellsderivedexosomesforimmunogenicchemotherapyofglioblastoma AT xuejiaoqi doxorubicinloadednanoparticlecoatedwithendothelialcellsderivedexosomesforimmunogenicchemotherapyofglioblastoma AT leizhao doxorubicinloadednanoparticlecoatedwithendothelialcellsderivedexosomesforimmunogenicchemotherapyofglioblastoma AT bofan doxorubicinloadednanoparticlecoatedwithendothelialcellsderivedexosomesforimmunogenicchemotherapyofglioblastoma AT guozhusun doxorubicinloadednanoparticlecoatedwithendothelialcellsderivedexosomesforimmunogenicchemotherapyofglioblastoma AT zhongqianglv doxorubicinloadednanoparticlecoatedwithendothelialcellsderivedexosomesforimmunogenicchemotherapyofglioblastoma AT zhenzengfan doxorubicinloadednanoparticlecoatedwithendothelialcellsderivedexosomesforimmunogenicchemotherapyofglioblastoma AT baohuajiao doxorubicinloadednanoparticlecoatedwithendothelialcellsderivedexosomesforimmunogenicchemotherapyofglioblastoma AT jiankaiyang doxorubicinloadednanoparticlecoatedwithendothelialcellsderivedexosomesforimmunogenicchemotherapyofglioblastoma |