Caspase 3 Targeted Cargo Delivery in Apoptotic Cells Using Capped Mesoporous Silica Nanoparticles |
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| Authors: | Cristina de la Torre Dr. Laura Mondragón Dr. Carmen Coll Alba García‐Fernández Dr. Félix Sancenón Prof. Ramón Martínez‐Máñez Prof. Pedro Amorós Dr. Mar Orzáez |
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| Affiliation: | 1. Centro de Reconocimiento Molecular y Desarrollo Tecnológico Unidad, Mixta Universidad Politécnica de Valencia Universidad de Valencia, Camino de Vera s/n, 46022, Valencia (Spain);2. Departamento de Química, Universidad Politécnica de Valencia, Camino de Vera s/n, 46022, Valencia (Spain);3. CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER‐BBN) (Spain);4. Centre Méditerranéen de Médecine Moléculaire (C3M) ‐ Equipe “Contr?le métabolique des morts cellulaires“, Université Nice Sophia Antipolis, Institut national de la santé et de la recherche médicale (Inserm), U1065, BP 2 3194, 06204, Nice (France);5. Institut de Ciéncia dels Materials (ICMUV), Universitat de Valéncia, P.O. Box 2085, 46071 Valencia (Spain);6. Peptide and Protein Laboratory, Department of Medicinal Chemistry, Centro de Investigación Principe Felipe, C/Eduardo Primo Yúfera 3, 46012 Valencia (Spain) |
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| Abstract: | 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. |
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| Keywords: | caspase 3 controlled release gated mesoporous materials nanoparticles peptides |
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