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Caspase 3 Targeted Cargo Delivery in Apoptotic Cells Using Capped Mesoporous Silica Nanoparticles

Cristina de la Torre1,2,3, Laura Mondragón1,2,3,4, Carmen Coll1,2,3

  • 1Centro de Reconocimiento Molecular y Desarrollo Tecnológico Unidad, Mixta Universidad Politécnica de Valencia Universidad de Valencia, Camino de Vera s/n, 46022, Valencia (Spain).

Chemistry (Weinheim an Der Bergstrasse, Germany)
|October 24, 2015
PubMed

Insights

New peptide-loaded nanoparticles offer a novel strategy to inhibit excessive apoptosis, a key factor in degenerative diseases and stroke. These systems target caspase-3 activation, presenting a potential therapeutic avenue for cell-death-related disorders.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cell Biology

Background:

  • Excessive apoptotic cell death contributes to various pathologies, including degenerative disorders and ischemia-reperfusion injury.
  • Targeting apoptosis pathways presents a potential pharmacological strategy for treating cell-death-related conditions.

Purpose of the Study:

  • To develop and evaluate novel peptide-containing delivery systems based on mesoporous silica nanoparticles (MSNs).
  • To investigate the potential of these systems in inhibiting apoptosis by targeting caspase-3 (C3).

Main Methods:

  • MSNs were loaded with a dye and functionalized with a peptide (P1) containing DEVD sequences, which are substrates for C3.
  • Two systems were synthesized: S1-P1 and S1-P2 (which included a TAT peptide for enhanced cell penetration).
  • HeLa cells were used to test cargo delivery and efficacy, with apoptosis induced by staurosporin (STS) or cisplatin.

Main Results:

  • S1-P1 nanoparticles delivered their cargo into HeLa cells upon C3 activation induced by STS.
  • S1-P2 nanoparticles, incorporating a TAT peptide, demonstrated enhanced cellular entry and preferential cargo delivery in cisplatin-treated cells.
  • The peptide P1's DEVD sequences were selectively hydrolyzed by C3, indicating targeted payload release.

Conclusions:

  • Peptide-functionalized MSNs are effective delivery systems for targeting apoptosis-related pathways.
  • The developed nanoparticles show promise as a therapeutic strategy for managing conditions associated with excessive apoptosis.
  • The incorporation of cell-penetrating peptides can enhance nanoparticle delivery and targeting efficiency.
Keywords:
caspase 3controlled releasegated mesoporous materialsnanoparticlespeptides

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