Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein.
Rossella De MarcoEnrico RampazzoJunwei ZhaoLuca ProdiMayra PaolilloPierre PicchettiFrancesca GalloNatalia CalonghiLuca GentilucciPublished in: Nanomaterials (Basel, Switzerland) (2020)
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.
Keyphrases
- cell cycle arrest
- cell death
- poor prognosis
- oxidative stress
- induced apoptosis
- pi k akt
- endoplasmic reticulum stress
- long non coding rna
- cell adhesion
- cell migration
- drug delivery
- quantum dots
- signaling pathway
- anti inflammatory
- amino acid
- binding protein
- cancer therapy
- protein protein
- photodynamic therapy
- cell proliferation
- cell therapy
- highly efficient
- bone marrow
- locally advanced
- dengue virus
- radiation therapy
- living cells
- high resolution
- zika virus
- label free
- tandem mass spectrometry