Caspase 3 Targeted Cargo Delivery in Apoptotic Cells Using Capped Mesoporous Silica Nanoparticles.
CHEMISTRY-A EUROPEAN JOURNAL(2015)
摘要
Excessive apoptotic cell death is at the origin of several pathologies, such as degenerative disorders, stroke or ischemia-reperfusion damage. In this context, strategies to improve inhibition of apoptosis and other types of cell death are of interest and may represent a pharmacological opportunity for the treatment of cell-death-related disorders. In this scenario new peptide-containing delivery systems (solids S-1-P-1 and S-1-P-2) are described based on mesoporous silica nanoparticles (MSNs) loaded with a dye and capped with the KKGDEVDKKARDEVDK (P-1) peptide that contains two repeats of the DEVD target sequence that are selectively hydrolyzed by caspase3 (C3). This enzyme plays a central role in the execution-phase of apoptosis. HeLa cells electroporated with S-1-P-1 are able to deliver the cargo in the presence of staurosporin (STS), which induces apoptosis with the consequent activation of the cytoplasmic C3 enzyme. Moreover, the nanoparticles S-1-P-2, containing both a cell-penetrating TAT peptide and P-1 also entered in HeLa cells and delivered the cargo preferentially in cells treated with the apoptosis inducer cisplatin.
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关键词
caspase3,controlled release,gated mesoporous materials,nanoparticles,peptides
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