ϵ‐Polylysine‐Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells

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Abstract
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 (C9h) 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 C9h 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 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/PP2Acα interaction.
Funding Information
  • Secretaría de Estado de Investigación, Desarrollo e Innovación (MAT2015-64139-C4-1, SAF2012-31405, SAF2015-67077-R, AGL2015-70235-C2-2-R)
  • Generalitat Valenciana (PROMETEOII/2014/047, PROMETEO/2012/061)

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