In addition to the intrinsic toxicity associated with the chemical composition of nanoparticles (NP) and their ligands, biofunctionalized NP can perturb specific cellular processes through NP-cell interactions and induce programmed cell death (apoptosis). In the case of the epidermal growth factor (EGF), nanoconjugation has been shown to enhance the apoptotic efficacy of the ligand, but the critical aspects of the underlying mechanism and its dependence on the NP morphology remain unclear. In this manuscript we characterize the apoptotic efficacy of nanoconjugated EGF as a function of NP size (with sphere diameters in the range 20-80 nm), aspect ratio (A.R., in the range of 4.5 to 8.6), and EGF surface loading in EGFR overexpressing MDA-MB-468 cells. We demonstrate a significant size and morphology dependence in this relatively narrow parameter space with spherical NP with a diameter of approx. 80 nm being much more efficient in inducing apoptosis than smaller spherical NP or rod-shaped NP with comparable EGF loading. The nanoconjugated EGF is found to trigger an EGFR-dependent increase in cytoplasmic reactive oxygen species (ROS) levels but no indications of increased mitochondrial ROS levels or mitochondrial membrane damage are detected at early time points of the apoptosis induction. The increase in cytoplasmic ROS is accompanied by a perturbation of the intracellular glutathione homeostasis, which represents an important check-point for NP-EGF mediated apoptosis. Abrogation of the oxidative stress through the inhibition of EGFR signaling by the EGFR inhibitor AG1478 or addition of antioxidants N-acetyl cysteine (NAC) or tempol, but not trolox, successfully suppressed the apoptotic effect of nanoconjugated EGF. A model to account for the observed morphology dependence of EGF nanoconjugation enhanced apoptosis and the underlying NP-cell interactions is discussed.
Noble metal nanoparticles have large cross-sections in both optical and electron microscopy and plasmon coupling between noble metal nanoparticles facilitate the characterization of subdiffraction limit separations through spectral analysis of the scattered light in Plasmon Coupling Microscopy (PCM). The size compatibility of noble metal nanoparticles together with the ability to encode specific functionality in a rational fashion by control of the nanoparticle surface makes noble metal nanoparticles unique probes for a broad range of biological processes. Recent applications of the technology include i.) characterization of cellular heterogeneity in nanomaterial uptake and processing through macrophages, ii.) testing the role of viral membrane lipids in mediating viral binding and trafficking, and iii.) characterizing the spatial organization of cancer biomarkers in plasma membranes. This paper reviews some of these applications and introduces the physical and material science principles underlying them. We will also introduce the use of membrane wrapped noble metal nanoparticles, which combine the superb photophysical properties of a nanoparticle core with the biological functionality of a membrane, as probes in PCM.
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