期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 58, 期 23, 页码 7657-7661出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201901699
关键词
antibody delivery; biodegradable; glutathione; mitochondrial targeting; protein delivery
资金
- GSK-EDB Trust Fund [R-143-000-688-592]
- Natural Science Foundation of China [81672508]
- Jiangsu Provincial Foundation for Distinguished Young Scholars [BK20170041]
- China-Sweden Joint Mobility Project [51811530018]
- MOE-T1 of Singapore [R-143-000-694-114]
Mitochondria are key organelles in mammalian cells whose dysfunction is linked to various diseases. Drugs targeting mitochondrial proteins provide a highly promising strategy for potential therapeutics. Methods for the delivery of small-molecule drugs to the mitochondria are available, but these are not suitable for macromolecules, such as proteins. Herein, we report the delivery of native proteins and antibodies to the mitochondria using biodegradable silica nanoparticles (BS-NPs). The modification of the nanoparticle surface with triphenylphosphonium (TPP) and cell-penetrating poly(disulfide)s (CPD) facilitated their rapid intracellular uptake with minimal endolysosomal trapping, providing sufficient time for effective mitochondrial localization followed by glutathione-triggered biodegradation and of native, functional proteins into the mitochondria.
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