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.
Integrin-targeting dye-doped peg-shell/silica-core nanoparticles mimicking the proapoptotic Smac/DIABLO protein / De Marco R.; Rampazzo E.; Zhao J.; Prodi L.; Paolillo M.; Picchetti P.; Gallo F.; Calonghi N.; Gentilucci L.. - In: NANOMATERIALS. - ISSN 2079-4991. - ELETTRONICO. - 10:6(2020), pp. 1211.1-1211.13. [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.File | Dimensione | Formato | |
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