ABSTRACT
A nanodelivery system based on palladium nanoparticles (PdNP) and cisplatin (CisPt) was developed by physisorption of the drug onto the PdNP synthesized via a green redox process, using d-glucose and polyvinylpyrrolidone (PVP) as reducing and stabilizing/capping agents, respectively. UV-vis analysis and H2-evolution measurements were carried out to prove the nanoparticles' capability to act as bimodal theranostic nanomedicine, i.e., having both plasmonic and photocatalytic properties. XPS, XRD, and TEM allowed light to be shed on the chemical composition and morphology of the PdNP. The analysis of the UV-visible spectra evidenced plasmonic peak changes for the hybrid nanoparticle-drug assembly (Pd@CisPt), which pointed to a significant interaction of CisPt with the NP surface. The drug loading was quantitatively estimated by ICP-OES measurements, while DLS and AFM confirmed the strong association of the drug with the nanoparticle surface. The test of SOD-like activity in a cell-free environment proved the maintenance of the antioxidant capability of PdNP also in the Pd@CisPt systems. Finally, Pd@CisPt tested in prostate cancer cells (PC-3 line) unveiled the antitumoral action of the developed nanomedicine, related to reactive oxygen species (ROS) generation, with a condition of protein misfolding/unfolding and DNA damage, as evidenced by cytotoxicity and MitoSOX assays, as well as Raman microspectroscopy, respectively. Cell imaging by confocal microscopy evidenced cellular uptake of the nanoparticles, as well as dynamic processes of copper ion accumulation at the level of subcellular compartments. Finally, cell migration studies upon treatment with Pd@CisPt evidenced a tunable response between the inhibitory effect of CisPt and the enhanced rate of cell migration for the metal NP alone, which pointed out the promising potential of the developed theranostic nanomedicine in tissue regeneration.
Subject(s)
Antineoplastic Agents , Metal Nanoparticles , Male , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Metal Nanoparticles/therapeutic use , Metal Nanoparticles/chemistry , Theranostic Nanomedicine/methods , Palladium/pharmacology , Palladium/chemistry , Cisplatin/chemistryABSTRACT
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
ABSTRACT
Angiogenin is a protein crucial in angiogenesis, and it is overexpressed in many cancers and downregulated in neurodegenerative diseases, respectively. The protein interaction with actin, through the loop encompassing the 60-68 residues, is an essential step in the cellular cytoskeleton reorganization. This, in turn, influences the cell proliferation and migration processes. In this work, hybrid nanoassemblies of gold nanoparticles with angiogenin fragments containing the 60-68 sequence were prepared and characterized in their interaction with both model membranes of supported lipid bilayers (SLBs) and cellular membranes of cancer (neuroblastoma) and normal (fibroblasts) cell lines. The comparison between physisorption and chemisorption mechanisms was performed by the parallel investigation of the 60-68 sequence and the peptide analogous containing an extra cysteine residue. Moreover, steric hindrance and charge effects were considered with a third analogous peptide sequence, conjugated with a fluorescent carboxyfluorescein (Fam) moiety. The hybrid nanobiointerface was characterized by means of ultraviolet-visible, atomic force microscopy and circular dichroism, to scrutinize plasmonic changes, nanoparticles coverage and conformational features, respectively. Lateral diffusion measurements on SLBs "perturbed" by the interaction with the gold nanoparticles-peptides point to a stronger membrane interaction in comparison with the uncoated nanoparticles. Cell viability and proliferation assays indicate a slight nanotoxicity in neuroblastoma cells and a proliferative activity in fibroblasts. The actin staining confirms different levels of interaction between the hybrid assemblies and the cell membranes.
Subject(s)
Angiogenesis Inducing Agents/metabolism , Cell Membrane/drug effects , Gold , Nanoparticles/chemistry , Peptides/metabolism , Ribonuclease, Pancreatic/metabolism , Cell Line , Cell Membrane/metabolism , Cell Survival/drug effects , Fibroblasts/drug effects , Fibroblasts/physiology , Humans , Nanoparticles/toxicity , Neurons/drug effects , Neurons/physiology , Protein BindingABSTRACT
The repeated use of conventional synthetic pesticides in crop protection leads to resistance development by pests along with a negative impact on the environment, particularly non-target arthropods. Plant-derived active compounds, such as essential oils (EOs), play a key role in sustainably controlling pests. The lethal and sublethal activity of citrus peel EOs as emulsions and included in polyethylene glycol (PEG) nanoparticles (EO-NPs) was determined against the invasive tomato pest Tuta absoluta. Their effects on the plants were also assessed. The results showed an overall good insecticidal activity of the compounds tested, with a higher mortality through contact on eggs and larvae by EO emulsions and through ingestion on larvae by EO-NPs. The nanoformulation also significantly reduced the visible toxic effects on the plants. The data collected suggest that these natural compounds, especially when nanoformulated, could be successfully used in integrated pest management programs for T. absoluta.
