| Title | LDL receptor-related protein 1 (LRP1), a novel target for opening the blood-labyrinth barrier (BLB) |
| Authors | Shi, Xi Wang, Zihao Ren, Wei Chen, Long Xu, Cong Li, Menghua Fan, Shiyong Xu, Yuru Chen, Mengbing Zheng, Fanjun Zhang, Wenyuan Zhou, Xinbo Zhang, Yue Qiu, Shiwei Wu, Liyuan Zhou, Peng Lv, Xinze Cui, Tianyu Qiao, Yuehua Zhao, Hui Guo, Weiwei Chen, Wei Li, Song Zhong, Wu Lin, Jian Yang, Shiming |
| Affiliation | Peking Univ Third Hosp, Dept Pharm, Beijing, Peoples R China Xuzhou Med Univ, Artificial Auditory Lab Jiangsu Prov, Xuzhou, Jiangsu, Peoples R China Beijing Inst Pharmacol & Toxicol, Natl Engn Res Ctr Emergency Drug, Beijing, Peoples R China Chinese Peoples Liberat Army Gen Hosp, Coll Otolaryngol Head & Neck Surg, Beijing, Peoples R China Natl Clin Res Ctr Otolaryngol Dis, Beijing, Peoples R China Minist Educ, Key Lab Hearing Sci, Beijing, Peoples R China Beijing Key Lab Hearing Impairment Prevent & Trea, Beijing, Peoples R China Peking Univ, Coll Chem & Mol Engn, Synthet & Funct Biomol Ctr,Beijing Natl Lab Mol S, Innovat Ctr Genom,Minist Educ,Key Lab Bioorgan Ch, Beijing, Peoples R China |
| Keywords | INNER-EAR GENE-THERAPY DELIVERY TRANSCYTOSIS CRISPR-CAS9 OTOTOXICITY CURCUMIN |
| Issue Date | 10-Jun-2022 |
| Publisher | SIGNAL TRANSDUCTION AND TARGETED THERAPY |
| Abstract | Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide. However, the presence of the blood-labyrinth barrier (BLB) on the surface of the inner ear capillaries greatly hinders the effectiveness of systemic drugs for prevention and intervention due to the low permeability, which restricts the entry of most drug compounds from the bloodstream into the inner ear tissue. Here, we report the finding of a novel receptor, low-density lipoprotein receptor-related protein 1 (LRP1), that is expressed on the BLB, as a potential target for shuttling therapeutics across this barrier. As a proof-of-concept, we developed an LRP1-binding peptide, IETP2, and covalently conjugated a series of model small-molecule compounds to it, including potential drugs and imaging agents. All compounds were successfully delivered into the inner ear and inner ear lymph, indicating that targeting the receptor LRP1 is a promising strategy to enhance the permeability of the BLB. The discovery of the receptor LRP1 will illuminate developing strategies for crossing the BLB and for improving systemic drug delivery for inner ear disorders. |
| URI | http://hdl.handle.net/20.500.11897/647759 |
| ISSN | 2095-9907 |
| DOI | 10.1038/s41392-022-00995-z |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 å å¦ä¸ å å å·¥ç¨ å¦é ¢ 生物有机与分子工程教育部重点实验室 |
