Anti-EGFR ScFv functionalized exosomes delivering LPCAT1 specific siRNAs for inhibition of lung cancer brain metastases

• Published in: Journal of nanobiotechnology 2024-04, Vol.22 (1), p.159-159, Article 159
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 1-Acylglycerophosphocholine O-acyltransferase; Acyltransferase; Analysis; Animal models; Animals; Antibodies; Biocompatibility; Blood-brain barrier; Brain cancer; Brain metastasis; Brain Neoplasms - pathology; Brain Neoplasms - therapy; Breast cancer; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - therapy; Care and treatment; Cell culture; Cell growth; Cell Line, Tumor; Cell proliferation; Diagnosis; Drug delivery; Drug delivery systems; Drug resistance; Drugs; Engineered exosomes; Enzymes; Epidermal growth factor receptors; ErbB Receptors - genetics; ErbB Receptors - metabolism; Evaluation; Exosomes; Exosomes - metabolism; Extracellular vesicles; Gene expression; Genes; Glioma; Growth factors; HEK293 Cells; Humans; Kinases; Lung cancer; Lung Neoplasms - metabolism; Lung Neoplasms - therapy; Lysophosphatidylcholine; Metastases; Metastasis; Non-small cell lung carcinoma; Penicillin; Permeability; Proteins; RNA; RNA, Small Interfering - pharmacology; RNA-mediated interference; siRNA; Small cell lung carcinoma; Toxicity; Up-regulation; Vehicles
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-024-02414-7

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 (exo ). 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.