Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein
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....
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/10/6/1211 |
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| author | Rossella De Marco Enrico Rampazzo Junwei Zhao Luca Prodi Mayra Paolillo Pierre Picchetti Francesca Gallo Natalia Calonghi Luca Gentilucci |
| author_facet | Rossella De Marco Enrico Rampazzo Junwei Zhao Luca Prodi Mayra Paolillo Pierre Picchetti Francesca Gallo Natalia Calonghi Luca Gentilucci |
| author_sort | Rossella De Marco |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T18:59:50Z |
| format | Article |
| id | doaj.art-fe0767e58bcd46318185dc54c8970534 |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-10T18:59:50Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-fe0767e58bcd46318185dc54c89705342023-11-20T04:31:48ZengMDPI AGNanomaterials2079-49912020-06-01106121110.3390/nano10061211Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO ProteinRossella De Marco0Enrico Rampazzo1Junwei Zhao2Luca Prodi3Mayra Paolillo4Pierre Picchetti5Francesca Gallo6Natalia Calonghi7Luca Gentilucci8Department of Agricultural, Food, Enviromental and Animal Sciences (DI4A), University of Udine, 33100 Udine, ItalyDepartment of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, ItalyDepartment of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, ItalyDepartment of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, ItalyDepartment of Drugs Sciences, University of Pavia, 27100 Pavia, ItalyInstitut de Science et d’Ingénierie Supramoléculaires (ISIS), Université de Strasbourg, 67083 Strasbourg, FranceDepartment of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, ItalyDepartment of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, ItalyDepartment of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, ItalyCancer 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.https://www.mdpi.com/2079-4991/10/6/1211Smac/DIABLOcancerRGDAVPIIAPconfocal microscopy |
| spellingShingle | Rossella De Marco Enrico Rampazzo Junwei Zhao Luca Prodi Mayra Paolillo Pierre Picchetti Francesca Gallo Natalia Calonghi Luca Gentilucci Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein Nanomaterials Smac/DIABLO cancer RGD AVPI IAP confocal microscopy |
| title | Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein |
| title_full | Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein |
| title_fullStr | Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein |
| title_full_unstemmed | Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein |
| title_short | Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein |
| title_sort | integrin targeting dye doped peg shell silica core nanoparticles mimicking the proapoptotic smac diablo protein |
| topic | Smac/DIABLO cancer RGD AVPI IAP confocal microscopy |
| url | https://www.mdpi.com/2079-4991/10/6/1211 |
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