LDL receptor-related protein 1 (LRP1), a novel target for opening the blood-labyrinth barrier (BLB)
Brief intro:
- Author: Xi Shi, Zihao Wang, Wei Ren, Long Chen, Cong Xu,Menghua Li, Shiyong Fan, Yuru Xu, Mengbing Chen, Fanjun Zheng, Wenyuan Zhang, Xinbo Zhou, Yue Zhang, Shiwei Qiu, Liyuan Wu, Peng Zhou, Xinze Lv, Tianyu Cui, Yuehua Qiao, Hui Zhao, Weiwei Guo, Wei Chen, Song Li, Wu Zhong, Jian Lin, and Shiming Yang
- Journal: Signal Transduct Target Ther
- Doi: https://www.doi.org/10.1038/s41392-022-00995-z
- Publication Date: 2022 Jun 10
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Quotation shows PackGene:The sequences of the plasmid for lentivirus (LV) construction, pLV- lenti.EFS.hspCas9.U6.sgRNA, were designed by PackGene Biotech (Guangzhou, China), and the LVs were packaged by the same company
Research Field:ear
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.
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