期刊
FRONTIERS IN CHEMISTRY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fchem.2021.736554
关键词
nucleolipid; nanocarrier; oil-in-water nanoemulsion; lysosome; pH; acidification; neurodegenerative disease
资金
- IDEX Emergence [OPE-2018-410]
Lysosomal dysfunction plays a pathogenic role in neurodegenerative diseases, with regulating lysosomal pH being a key factor in combating neurodegeneration. Crossing the Blood-Brain-Barrier is crucial for developing chronic treatments for neurodegenerative diseases.
Increasing evidence suggests that lysosomal dysfunction has a pathogenic role in neurodegenerative diseases. In particular, an increase in lysosomal pH has been reported in different cellular models of Parkinson's disease. Thus, targeting lysosomes has emerged as a promising approach. More specifically, regulating its pH could play a central role against the neurodegeneration process. To date, only a few agents specifically targeting lysosomal pH are reported in the literature, partly due to the challenge of crossing the Blood-Brain-Barrier (BBB), preventing drug penetration into the central nervous system (CNS). To develop chronic treatments for neurodegenerative diseases, crossing the BBB is crucial. We report herein the conception and synthesis of an innovative DNA derivative-based nanocarrier. Nucleolipids, carrying a biocompatible organic acid as an active ingredient, were designed and synthesized as prodrugs. They were successfully incorporated into an oil-in-water nanoemulsion vehicle to cross biological membranes and then release effectively biocompatible acidic components to restore the functional lysosomal pH of neuronal cells. Biological assays on a genetic cell model of Parkinson's disease highlighted the non-toxicity of such nucleolipids after cellular uptake and their ability (at c = 40 mu M) to fully restore lysosomal acidity.
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