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ϵ ‐Polylysine‐Capped Mesoporous Silica Nanoparticles as Carrier of the C 9 h Peptide to Induce Apoptosis in Cancer Cells
Author(s) -
de la Torre Cristina,
DomínguezBerrocal Leticia,
Murguía José R.,
Marcos M. Dolores,
MartínezMáñez Ramón,
Bravo Jerónimo,
Sancenón Félix
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201704161
Subject(s) - hela , apoptosis , peptide , annexin , polylysine , chemistry , mesoporous silica , cancer cell , biophysics , flow cytometry , microbiology and biotechnology , biochemistry , cell , biology , mesoporous material , cancer , genetics , catalysis
Apoptotic signaling pathways are altered in numerous pathologies such as cancer. In this scenario, caspase‐9/PP2Acα interaction constitutes a key target with pharmacological interest to re‐establish apoptosis in tumor cells. Very recently, a short peptide ( C 9 h ) known to disrupt caspase‐9/PP2Acα interaction with subsequent apoptosis induction was described. Here, we prepared two sets of mesoporous silica nanoparticles loaded with safranin O ( S2 ) or with C 9 h peptide ( S4 ) and functionalized with ϵ ‐polylysine as capping unit. Aqueous suspensions of both nanoparticles showed negligible cargo release whereas in the presence of pronase, a marked delivery of safranin O or C 9 h 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 C 9 h ‐loaded S4 nanoparticles. Moreover, S4 provides peptide protection from degradation additionally allowing for a dose reduction to observe an apoptotic effect when compared with C 9 h alone or in combination with a cell‐penetrating peptide (i.e., Mut3DPT‐ C 9 h ). 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 C 9 h peptide and disruption of caspase‐9/PP2Acα interaction.