微泡
肺癌
下调和上调
癌症研究
小干扰RNA
转移
基因沉默
RNA干扰
体内
生物
表皮生长因子受体
癌症
小RNA
细胞培养
医学
核糖核酸
病理
转染
生物化学
遗传学
生物技术
基因
作者
Jun Jiang,Linhong Yuan,Jie Chu,Xiao Zhang,Cheng Xu,Shaojie Li,Zhuo Wan,Jiawei Wang,Lu Zhang,Liu Kui,Zhenhua Liu,An‐Gang Yang,Xue Ren,Rui Zhang
标识
DOI:10.1186/s12951-024-02414-7
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI