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De Marco R, Rampazzo E, Zhao J, et al. Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein. Nanomaterials (Basel). 2020;10(6)doi: 10.3390/nano10061211.
De Marco, R., Rampazzo, E., Zhao, J., Prodi, L., Paolillo, M., Picchetti, P., Gallo, F., Calonghi, N., & Gentilucci, L. (2020). Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein. Nanomaterials (Basel, Switzerland), 10(6), . https://doi.org/10.3390/nano10061211
De Marco, Rossella, et al. "Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein." Nanomaterials (Basel, Switzerland) vol. 10,6 (2020). doi: https://doi.org/10.3390/nano10061211
De Marco R, Rampazzo E, Zhao J, Prodi L, Paolillo M, Picchetti P, Gallo F, Calonghi N, Gentilucci L. Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein. Nanomaterials (Basel). 2020 Jun 21;10(6). doi: 10.3390/nano10061211. PMID: 32575872; PMCID: PMC7353088.
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Nanomaterials (Basel). 2020 Jun 21;10(6). doi: 10.3390/nano10061211.

Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein.

Nanomaterials (Basel, Switzerland)

Rossella De Marco, Enrico Rampazzo, Junwei Zhao, Luca Prodi, Mayra Paolillo, Pierre Picchetti, Francesca Gallo, Natalia Calonghi, Luca Gentilucci

Affiliations

  1. Department of Agricultural, Food, Enviromental and Animal Sciences (DI4A), University of Udine, 33100 Udine, Italy.
  2. Department of Chemistry "G. Ciamician", University of Bologna, 40126 Bologna, Italy.
  3. Department of Drugs Sciences, University of Pavia, 27100 Pavia, Italy.
  4. Institut de Science et d'Ingénierie Supramoléculaires (ISIS), Université de Strasbourg, 67083 Strasbourg, France.
  5. Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy.

PMID: 32575872 PMCID: PMC7353088 DOI: 10.3390/nano10061211

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.

Keywords: AVPI; IAP; RGD; Smac/DIABLO; cancer; cellular uptake; confocal microscopy; drug delivery; silica nanoparticles

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