epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells
| Autor: | M. Dolores Marcos, José Ramón Murguía, Leticia Dominguez-Berrocal, Jerónimo Bravo, Cristina de la Torre, Ramón Martínez-Máñez, Félix Sancenón |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Peptide
Apoptosis 02 engineering and technology 010402 general chemistry 01 natural sciences Catalysis Gated nanoparticles HeLa chemistry.chemical_compound QUIMICA ORGANICA Annexin QUIMICA ANALITICA BIOQUIMICA Y BIOLOGIA MOLECULAR Humans Polylysine Viability assay Amino Acid Sequence Protein Phosphatase 2 chemistry.chemical_classification Drug Carriers Microscopy Confocal biology Chemistry Circular Dichroism Organic Chemistry QUIMICA INORGANICA General Chemistry Mesoporous silica 021001 nanoscience & nanotechnology biology.organism_classification Silicon Dioxide Caspase 9 0104 chemical sciences Drug delivery Cancer cell Biophysics Nanoparticles Phenazines 0210 nano-technology Peptides Porosity Caspase-9 HeLa Cells |
| Zdroj: | RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia instname |
| ISSN: | 2015-6413 |
| DOI: | 10.1002/chem.201704161 |
| Popis: | [EN] Apoptotic signaling pathways are altered in numerous pathologies such as cancer. In this scenario, caspase-9/PP2Ac alpha interaction constitutes a key target with pharmacological interest to re-establish apoptosis in tumor cells. Very recently, a short peptide (C9h) known to disrupt caspase-9/PP2Ac alpha interaction with subsequent apoptosis induction was described. Here, we prepared two sets of mesoporous silica nanoparticles loaded with safraninO (S2) or with C9h peptide (S4) and functionalized with epsilon-polylysine as capping unit. Aqueous suspensions of both nanoparticles showed negligible cargo release whereas in the presence of pronase, a marked delivery of safraninO or C9h was observed. Confocal microscopy studies carried out with HeLa cells indicated that both materials were internalized and were able to release their entrapped cargos. Besides, a marked decrease in HeLa cell viability (ca. 50%) was observed when treated with C9h-loaded S4 nanoparticles. Moreover, S4 provides peptide protection from degradation additionally allowing for a dose reduction to observe an apoptotic effect when compared with C9h alone or in combination with a cell-penetrating peptide (i.e., Mut3DPT-C9h). Flow cytometry studies, by means of Annexin V-FITC staining, showed the activation of apoptotic pathways in HeLa as a consequence of S4 internalization, release of C9h peptide and disruption of caspase-9/PP2Ac alpha interaction. The authors wish to express their gratitude to the Spanish government (Projects MAT2015-64139-C4-1, SAF2012-31405, SAF2015-67077-R, AGL2015-70235-C2-2-R (MINECO/FEDER)), the Generalitat Valencia (Projects PROMETEOII/2014/047, PROMETEO/2012/061) and the CIBER-BBN for their support. C.T. is grateful to the Spanish Ministry of Science and Innovation for her Ph.D. fellowship. |
| Databáze: | OpenAIRE |
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