PUBLICATION
Inflammatory tumor microenvironment responsive neutrophil exosomes-based drug delivery system for targeted glioma therapy
- Authors
- Wang, J., Tang, W., Yang, M., Yin, Y., Li, H., Hu, F., Tang, L., Ma, X., Zhang, Y., Wang, Y.
- ID
- ZDB-PUB-210414-7
- Date
- 2021
- Source
- Biomaterials 273: 120784 (Journal)
- Registered Authors
- Keywords
- Blood brain barrier, Exosomes, Glioma, Neutrophils, Tumor microenvironment
- MeSH Terms
-
- Animals
- Blood-Brain Barrier
- Brain Neoplasms*/drug therapy
- Cell Line, Tumor
- Doxorubicin/therapeutic use
- Drug Delivery Systems
- Exosomes*
- Glioma*/drug therapy
- Mice
- Neutrophils
- Tumor Microenvironment
- Zebrafish
- PubMed
- 33848731 Full text @ Biomaterials
Citation
Wang, J., Tang, W., Yang, M., Yin, Y., Li, H., Hu, F., Tang, L., Ma, X., Zhang, Y., Wang, Y. (2021) Inflammatory tumor microenvironment responsive neutrophil exosomes-based drug delivery system for targeted glioma therapy. Biomaterials. 273:120784.
Abstract
Clinical treatment of malignant glioma remains a major challenge due to high infiltrative growth and chemotherapeutic resistance of tumors and the presence of the blood brain barrier (BBB). Advanced nanoplatforms that can efficiently cross the BBB and target to brain tumor are urgently needed. Encouraged by the intrinsic inflammatory chemotaxis and excellent BBB-crossing capability of neutrophils, a bioinspired neutrophil-exosomes (NEs-Exos) system for delivering loaded doxorubicin (DOX) drug for glioma treatment is proposed and systematically investigated. In vivo zebrafish and C6-Luc glioma-bearing mice models show that NEs-Exos carrying the drug rapidly penetrate the BBB and migrate into the brain. Additionally, a transwell BBB model and mouse brain inflammatory study show that NEs-Exos can respond chemotactically to inflammatory stimuli and target infiltrating tumor cells in inflamed brain tumors. Moreover, intravenous injection of NEs-Exos/DOX efficiently suppress tumor growth and prolong survival time in a glioma mouse model. On the basis of these results, NEs-Exos are confirmed to have neutrophil-like chemotactic function and BBB penetration. This novel NEs-Exos/DOX delivery platform represents a promising chemotherapeutic approach for clinical treatment of glioma and other solid tumor or brain diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping