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

[EN] 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 opportu...

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Detalles Bibliográficos
Autores: De la Torre Paredes, Cristina, Mondragón Martínez, Laura, Coll Merino, Mª Carmen, Amorós, Pedro, Pérez Payá, Enrique, Orzáez, Mar, García-Fernández, Alba|||0000-0002-8416-1674, Sancenón Galarza, Félix|||0000-0002-5205-7135, Martínez-Máñez, Ramón|||0000-0001-5873-9674
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universitat Politècnica de València (UPV)
Repositorio:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:inglés
OAI Identifier:oai:riunet.upv.es:10251/150334
Acceso en línea:https://riunet.upv.es/handle/10251/150334
Access Level:acceso abierto
Palabra clave:Caspase 3
Controlled release
Gated mesoporous materials
Nanoparticles
Peptides
QUIMICA ORGANICA
BIOQUIMICA Y BIOLOGIA MOLECULAR
QUIMICA ANALITICA
QUIMICA INORGANICA
Descripción
Sumario:[EN] 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-P1and S1-P2) are described based on meso-porous 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 caspase3 (C3). This enzyme plays a central role in the execution-phase of apoptosis. HeLa cells electroporated with S1 P1are 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.

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