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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Jiang, Jun Lu, Yuan Chu, Jie Zhang, Xiao Xu, Chao Liu, Shaojie Wan, Zhuo Wang, Jiawei Zhang, Lu Liu, Kui Liu, Zhenhua Yang, Angang Ren, Xinling Zhang, Rui |
| Abstract | Brain metastasis (BM) is one of the leading causes of cancer-related deaths in patients with advanced non-small cell lung cancer (NSCLC). However, limited treatments are available due to the presence of the blood-brain barrier (BBB). Upregulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) in NSCLC has been found to promote BM. Conversely, downregulating LPCAT1 significantly suppresses the proliferation and metastasis of lung cancer cells. In this study, we firstly confirmed significant upregulation of LPCAT1 in BM sites compared to primary lung cancer by analyzing scRNA dataset. We then designed a delivery system based on a single-chain variable fragment (scFv) targeting the epidermal growth factor receptor (EGFR) and exosomes derived from HEK293T cells to enhance cell-targeting capabilities and increase permeability. Next, we loaded LPCAT1 siRNA (siLPCAT1) into these engineered exosomes (exoscFv). This novel scFv-mounted exosome successfully crossed the BBB in an animal model and delivered siLPCAT1 to the BM site. Silencing LPCAT1 efficiently arrested tumor growth and inhibited malignant progression of BM in vivo without detectable toxicity. Overall, we provided a potential platform based on exosomes for RNA interference (RNAi) therapy in lung cancer BM. |
| Related Links | https://jnanobiotechnology.biomedcentral.com/counter/pdf/10.1186/s12951-024-02414-7.pdf |
| Ending Page | 16 |
| Page Count | 16 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14773155 |
| DOI | 10.1186/s12951-024-02414-7 |
| Journal | Journal of Nanobiotechnology |
| Issue Number | 1 |
| Volume Number | 22 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-04-08 |
| Access Restriction | Open |
| Subject Keyword | Biotechnology Nanotechnology Molecular Medicine Lung cancer Engineered exosomes Drug delivery Brain metastasis Blood-brain barrier |
| Content Type | Text |
| Resource Type | Article |
| Subject | Bioengineering Pharmaceutical Science Medicine Applied Microbiology and Biotechnology Biomedical Engineering Molecular Medicine Nanoscience and Nanotechnology |
| Journal Impact Factor | 10.6/2023 |
| 5-Year Journal Impact Factor | 11.4/2023 |
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