Cancer cells demonstrate elevated expression levels of the inhibitor of apoptosis proteins (IAPs), contributing to tumor cell survival, disease progression, chemo-resistance, and poor prognosis. Smac/DIABLO is a mitochondrial protein that promotes apoptosis by neutralizing members of the IAP family. Herein, we describe the preparation and in vitro validation of a synthetic mimic of Smac/DIABLO, based on fluorescent polyethylene glycol (PEG)-coated silica-core nanoparticles (NPs) carrying a Smac/DIABLO-derived pro-apoptotic peptide and a tumor-homing integrin peptide ligand. At low µM concentration, the NPs showed significant toxicity towards A549, U373, and HeLa cancer cells and modest toxicity towards other integrin-expressing cells, correlated with integrin-mediated cell uptake and consequent highly increased levels of apoptotic activity, without perturbing cells not expressing the α5 integrin subunit.

De Marco R., Rampazzo E., Zhao J., Prodi L., Paolillo M., Picchetti P., et al. (2020). Integrin-targeting dye-doped peg-shell/silica-core nanoparticles mimicking the proapoptotic Smac/DIABLO protein. NANOMATERIALS, 10(6), 1-13 [10.3390/nano10061211].

Integrin-targeting dye-doped peg-shell/silica-core nanoparticles mimicking the proapoptotic Smac/DIABLO protein

De Marco R.;Rampazzo E.;Zhao J.;Prodi L.;Calonghi N.
;
Gentilucci L.
2020

Abstract

Cancer cells demonstrate elevated expression levels of the inhibitor of apoptosis proteins (IAPs), contributing to tumor cell survival, disease progression, chemo-resistance, and poor prognosis. Smac/DIABLO is a mitochondrial protein that promotes apoptosis by neutralizing members of the IAP family. Herein, we describe the preparation and in vitro validation of a synthetic mimic of Smac/DIABLO, based on fluorescent polyethylene glycol (PEG)-coated silica-core nanoparticles (NPs) carrying a Smac/DIABLO-derived pro-apoptotic peptide and a tumor-homing integrin peptide ligand. At low µM concentration, the NPs showed significant toxicity towards A549, U373, and HeLa cancer cells and modest toxicity towards other integrin-expressing cells, correlated with integrin-mediated cell uptake and consequent highly increased levels of apoptotic activity, without perturbing cells not expressing the α5 integrin subunit.
2020
De Marco R., Rampazzo E., Zhao J., Prodi L., Paolillo M., Picchetti P., et al. (2020). Integrin-targeting dye-doped peg-shell/silica-core nanoparticles mimicking the proapoptotic Smac/DIABLO protein. NANOMATERIALS, 10(6), 1-13 [10.3390/nano10061211].
De Marco R.; Rampazzo E.; Zhao J.; Prodi L.; Paolillo M.; Picchetti P.; Gallo F.; Calonghi N.; Gentilucci L.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/787828
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