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

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.

Mesoporous Silica‐Based Materials with Bactericidal Properties

“…Moreover, the pore‐blockers should respond to appropriate external or internal triggers to close or open the well‐defined pores, causing on‐demand intelligent cargo delivery . Various porekeepers including polymers (e.g., polymer poly(2‐vinylpyridine) (PVP), poly(N‐succinimidyl acrylate), poly(2‐dimethylaminoethyl methacrylate), poly(acrylic acid) brush), host–guest assemblies (e.g., Cyclodextrins, cucurbit,uril, pillararenes), inorganic nanomaterials (e.g., Au NPs, quantum dots, Ag NPs, cerium oxide NPs, manganese oxide NPs, and reduced graphene), and biomacromolecules (e.g., peptides, nucleic acids, saccharides, and proteins) have been employed under certain internal or external stimuli, such as pH, temperature, light, redox potential, ultrasound, small molecules, biomolecules, and or a combination of these stimuli, to achieve controllable DDSs based on mesoporous silica nanoparticles (MSNs) …”

Ultrasound responsive mesoporous silica nanoparticles for biomedical applications

“…13 Since then, a great variety of therapeutic agents have been loaded into MSMs for different biomedical applications, such as drug delivery, imaging or theranostics. 16,17,18,19,20,21,22,23…”

Janus Gold Nanostars–Mesoporous Silica Nanoparticles for NIR‐Light‐Triggered Drug Delivery

“…One of the most studied applications of these gated systems is their use as nanodevices for controlled drug delivery . Among different stimuli, nanodevices for controlled release in response to light irradiation are particularly appealing since cargo delivery can be triggered at will by choosing the area and time of irradiation .…”

“…[6] One of the most studied applications of these gated systems is their use as nanodevicesf or controlled drugd elivery. [7][8][9][10][11][12] Amongd ifferent stimuli, nanodevicesf or controlled releasei n responset ol ight irradiation are particularly appealing since cargo delivery can be triggered at will by choosing the area and time of irradiation. [13,14] Moreover,t he design of nanodevices able to release an entrapped drug by using near infrared (NIR)l ight have remarkable interestd ue to the high penetrationo fN IR radiation and minimal damage to tissues.…”