GRP94 mediates blood-brain barrier permeation and substantia nigra-specific drug distribution in Parkinson’s disease

IF 5.4 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces Pub Date : 2025-02-19 DOI:10.1016/j.colsurfb.2025.114585

Ziyan Lv , Yuteng Zeng , Taiyong Lv , Qiao Liu , Liang Han

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引用次数: 0

Abstract

Parkinson’s disease is a progressive neurodegenerative disorder, which is characterized by pathological changes and progressive loss of dopaminergic neurons in the substantia nigra, e.g., endoplasmic reticulum stress. The blood-brain barrier (BBB) restricts the intracranial drug concentration and the therapeutic outcomes to a remarkable degree. Receptor-mediated transport has been extensively leveraged to design brain-targeting drug delivery systems to enhance intracranial drug levels. However, the target receptors at the BBB are widely expressed in normal brain parenchymal cells, which would affect drug distribution in local diseased brain regions, e.g., the substantia nigra in Parkinson’s disease. Here, we found glucose-regulated protein 94 (GRP94), as an endoplasmic reticulum resident protein, is upregulated at the surface of substantia nigra neurons in Parkinson’s disease. Considering that GRP94 could function like receptors to trigger cellular endocytosis and transcytosis, we constructed GRP94-specific peptide ligand NGPTHE-modified N-NPs and found that N-NPs could specially deliver drugs to the locally affected substantia nigra in Parkinson’s disease. This study provides a GRP94-based proof-of-concept strategy for specific drug delivery for Parkinson’s disease.

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来源期刊

Colloids and Surfaces B: Biointerfaces 生物-材料科学：生物材料

CiteScore

11.10

自引率

3.40%

发文量

730

审稿时长

42 days

期刊介绍： Colloids and Surfaces B: Biointerfaces is an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin, having particular relevance to the medical, pharmaceutical, biotechnological, food and cosmetic fields. Submissions that: (1) deal solely with biological phenomena and do not describe the physico-chemical or colloid-chemical background and/or mechanism of the phenomena, and (2) deal solely with colloid/interfacial phenomena and do not have appropriate biological content or relevance, are outside the scope of the journal and will not be considered for publication. The journal publishes regular research papers, reviews, short communications and invited perspective articles, called BioInterface Perspectives. The BioInterface Perspective provide researchers the opportunity to review their own work, as well as provide insight into the work of others that inspired and influenced the author. Regular articles should have a maximum total length of 6,000 words. In addition, a (combined) maximum of 8 normal-sized figures and/or tables is allowed (so for instance 3 tables and 5 figures). For multiple-panel figures each set of two panels equates to one figure. Short communications should not exceed half of the above. It is required to give on the article cover page a short statistical summary of the article listing the total number of words and tables/figures.