Caspase 3 Targeted Cargo Delivery in Apoptotic Cells Using Capped Mesoporous Silica Nanoparticles

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...

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Bibliographic Details
Published in:Chemistry : a European journal 2015-10, Vol.21 (44), p.15506-15510
Main Authors: de la Torre, Cristina, Mondragón, Laura, Coll, Carmen, García-Fernández, Alba, Sancenón, Félix, Martínez-Máñez, Ramón, Amorós, Pedro, Pérez-Payá, Enrique, Orzáez, Mar
Format: Article
Language:English
Subjects:
Apoptosis
Capping
Cargo
Caspase 3 - chemistry
Caspase 3 - metabolism
caspase 3
Cell death
Chemistry
Cisplatin - chemistry
controlled release
Disorders
Drug Carriers - chemistry
Drug Carriers - metabolism
Enzymes
gated mesoporous materials
HeLa Cells
Humans
Nanoparticles
Nanoparticles - chemistry
Peptides
Porosity
Silicon Dioxide - chemistry
Silicon Dioxide - metabolism
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Summary: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 S1‐P1 and S1‐P2) are described based on mesoporous silica nanoparticles (MSNs) loaded with a dye and capped with the KKGDEVDKKARDEVDK (P1) peptide that contains two repeats of the DEVD target sequence that are selectively hydrolyzed by caspase 3 (C3). This enzyme plays a central role in the execution‐phase of apoptosis. HeLa cells electroporated with S1–P1 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 S1‐P2, containing both a cell‐penetrating TAT peptide and P1 also entered in HeLa cells and delivered the cargo preferentially in cells treated with the apoptosis inducer cisplatin. Controlled release: S1‐P1 and S1‐P2 nanoparticles capped with a peptide sequence recognized and hydrolyzed by caspase 3 enzyme were synthesized and characterized. In vitro and ex vivo studies of both materials proved the caspase 3 induced release of the entrapped dye (see scheme).
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.201502413