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Nanoparticle (NP) colloidal stability plays a crucial role in biomedical application not only for human and environmental safety but also for NP efficiency and functionality. NP agglomeration is considered as a possible process in monodispersed NP colloidal solutions, which drastically affects colloidal stability. This process is triggered by changes in the physicochemical properties of the surrounding media, such as ionic strength (IS), pH value, or presence of biomolecules. Despite different available characterization methods for nanoparticles (NPs), there is a lack of information about the underlying mechanisms at the early stage of dynamic behaviors, namely changing in NP size distribution and structure while placing them from a stable colloidal solution to a new media like biological fluids. In this study, an advancedin situapproach is presented that combines small angle X-ray scattering (SAXS) and microfluidics, allowing label-free, direct, time-resolved, and dynamic observations of the early stage of NP interaction/agglomeration initiated by environmental changes. It is shown for silica NPs that the presence of protein in the media enormously accelerates the NP agglomeration process compared to respective changes in IS and pH. High IS results in a staring agglomeration process after 40 min, though, in case of protein presence in media, this time decreased enormously to 48 s. These time scales show that this method is sensitive and precise in depicting the dynamics of fast and slow NP interactions in colloidal conditions and therefore supports understanding the colloidal stability of NPs in various media concluding in safe and efficient NP designing for various applications., Nano Research, 13 (10), ISSN:1998-0000, ISSN:1998-0124

The COVID-19 outbreak has fueled a global demand for effective diagnosis and treatment as well as mitigation of the spread of infection, all through large-scale approaches such as specific alternative antiviral methods and classical disinfection protocols. Based on an abundance of engineered materials identifiable by their useful physicochemical properties through versatile chemical functionalization, nanotechnology offers a number of approaches to cope with this emergency. Here, through a multidisciplinary Perspective encompassing diverse fields such as virology, biology, medicine, engineering, chemistry, materials science, and computational science, we outline how nanotechnology-based strategies can support the fight against COVID-19, as well as infectious diseases in general, including future pandemics. Considering what we know so far about the life cycle of the virus, we envision key steps where nanotechnology could counter the disease. First, nanoparticles (NPs) can offer alternative methods to classical disinfection protocols used in healthcare settings, thanks to their intrinsic antipathogenic properties and/or their ability to inactivate viruses, bacteria, fungi, or yeasts either photothermally or via photocatalysis-induced reactive oxygen species (ROS) generation. Nanotechnology tools to inactivate SARS-CoV-2 in patients could also be explored. In this case, nanomaterials could be used to deliver drugs to the pulmonary system to inhibit interaction between angiotensin-converting enzyme 2 (ACE2) receptors and viral S protein. Moreover, the concept of “nanoimmunity by design” can help us to design materials for immune modulation, either stimulating or suppressing the immune response, which would find applications in the context of vaccine development for SARS-CoV-2 or in counteracting the cytokine storm, respectively. In addition to disease prevention and therapeutic potential, nanotechnology has important roles in diagnostics, with potential to support the development of simple, fast, and cost-effective nanotechnology-based assays to monitor the presence of SARS-CoV-2 and related biomarkers. In summary, nanotechnology is critical in counteracting COVID-19 and will be vital when preparing for future pandemics., L.G.D. acknowledges the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 734381 (CARBOimmap), and the University of Padua (Italy) DOR-2020. A.Y. is thankful to the Turkish Academy of Sciences (TUBA) for financial support under the young investigator programme. A.M. thanks funding by the CERCA programme/Generalitat de Catalunya and the Severo Ochoa Centres of Excellence programme and by the Spanish Research Agency (AEI, Grant No. SEV-2017-0706) given to ICN2. C.M. would like to acknowledge the award of funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No. 819069) and the award of a Royal Society University Research Fellowship (UF160539) by the UK Royal Society. Y.G. was supported by the U.S. National Science Foundation under Grant No. DMR-1740795. M.C. acknowledges the Labex SERENADE funded by the “Investissements d’Avenir” French Government program of the French National Research Agency (Grant No. ANR-11-LABX-0064) through the A*MIDEX project (Grant No. ANR-11-IDEX-0001-02).

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. In ALS mice, neurodegeneration is associated with the proliferative restorative attempts of ependymal stem progenitor cells (epSPCs) that normally lie in a quiescent in the spinal cord. Thus, modulation of the proliferation of epSPCs may represent a potential strategy to counteract neurodegeneration. Recent studies demonstrated that FM19G11, a hypoxia-inducible factor modulator, induces epSPC self-renewal and proliferation. The aim of the study was to investigate whether FM19G11-loaded gold nanoparticles (NPs) can affect self-renewal and proliferation processes in epSPCs isolated from G93A-SOD1 mice at disease onset. We discovered elevated levels of SOX2, OCT4, AKT1, and AKT3, key genes associated with pluripotency, self-renewal, and proliferation, in G93A-SOD1 epSPCs at the transcriptional and protein levels after treatment with FM19G11-loaded NPs. We also observed an increase in the levels of the mitochondrial uncoupling protein (UCP) gene in treated cells. FM19G11-loaded NPs treatment also affected the expression of the cell cycle-related microRNA (miR)-19a, along with its target gene PTEN, in G93A-SOD1 epSPCs. Overall our findings establish the significant impact of FM19G11-loaded NPs on the cellular pathways involved in self-renewal and proliferation in G93A-SOD1 epSPCs, thus providing an impetus to the design of novel tailored approaches to delay ALS disease progression.

The development of synthetic nanomaterials that could embed within, penetrate, or induce fusion between membranes without permanent disruption would have great significance for biomedical applications. Here we describe structure-function relationships of highly water-soluble gold nanoparticles comprised of an ∼1.5-5 nm diameter metal core coated by an amphiphilic organic ligand shell, which exhibit membrane embedding and fusion activity mediated by the surface ligands. Using an environment-sensitive dye anchored within the ligand shell as a sensor of membrane embedding, we demonstrate that particles with core sizes of ∼2-3 nm are capable of embedding within and penetrating fluid bilayers. At the nanoscale, these particles also promote spontaneous fusion of liposomes or spontaneously embed within intact liposomal vesicles. These studies provide nanoparticle design and selection principles that could be used in drug delivery applications, as membrane stains, or for the creation of novel organic/inorganic nanomaterial self-assemblies.

Hybrid colloidal nanocomposites comprising polystyrene beads and plasmonic gold nanostars are reported as multifunctional optical nanoprobes. Such self-assembled structures are excellent Raman enhancers for bioapplications as they feature plasmon modes in the near-infrared "first biological transparency window". In this proof of concept study, we used 4-mercaptobenzoic acid as a Raman-active molecule to optimize the density of gold nanostars on polystyrene beads, improving SERS performance and thereby allowing in vitro cell culture imaging. Interestingly, intermediate gold nanostar loadings were found to yield higher SERS response, which was confirmed by electromagnetic modeling. These engineered hybrid nanostructures notably improve the possibilities of using gold nanostars as SERS tags. Additionally, when fluorescently labeled polystyrene beads are used as colloidal carriers, the composite particles can be applied as promising tools for multimodal bioimaging. © 2016 American Chemical Society.

One of the tremendous areas of growth on the research side involves using nanomaterials both as imaging agents and as drug delivery vehicles. Nuclear magnetic resonance imaging (MRI) is a particular attractive imagin modality: it provides high-resolution, detailed structural images, three-dimensional spatial reconstruction, and no ionizing radiation.[1] Moreover, MRI is superior to optical bio-imaging in living systems for the visualization of deep tissues. 1H and 19F are the most sensitive nucleai for MRI, with the 1H signal suited for collecting information about the body for diagnostic purposes due to its high sensitivity. However, 1H MRI often suffers from a low contrast-to-noise ratio because of the large background signals from water protons. Therefore, for specific imaging both in vivo and ex vivo, there is still an obvious need to develop new methodologies. In particular, 19F holds great promise as an alternative nuclide for MRI as it is highly sensitive in nuclear magnetic resonance (NMR) spectroscopy (83% relative to 1H) and has 100% natural abundance. A more important advantage of 19F is that in animal bodies essentially no endogenous 19F is detectable by MRI, which therefore eliminates interference from background signals. Moreover, unlike other prototypical metal-based contrast agents, 19F MRI also enables image quantification.[2] As 19F imaging agents, a variety of fluorinated small molecule compounds have been proposed, perfluoro-15-crown-5-ether (PFCE) or perfluorobenzene (PFB) being the most commonly used perfluorocarbons (PFCs) in 19F-MRI research. These PFC molecules have poor solubility in water and, as such, are typically emulsified into lipid micro/NP formulations for biological applications. Moreover, such lipid-based formulations sometimes have drawbacks, which limit imaging capabilities to the vasculature with intravenous administration. In the last years we have reported examples of water soluble gold nanoparticles (NPs) protected by homoligand and heteroligand fluorinated-/hydrogenated ligands.[3] We will reported in this communication the design, synthesis, and characterization of gold nanoparticles (NPs) protected by fluorinated ligands which are endowed with 19F NMR properties suitable for applications in diagnostic imaging. Considering that gold NPs are excellent scaffold for medical uses and that they can be easily modified introducing pro(drugs) and specific recognition elements, our fluorinated NPs may behave both as imaging and therapeutic agents.

The deposition of amyloid-&beta, (A&beta, ) plaques in the brain is a significant pathological signature of Alzheimer&rsquo, s disease, correlating with synaptic dysfunction and neurodegeneration. Several compounds, peptides, or drugs have been designed to redirect or stop A&beta, aggregation. Among them, the trideca-peptide CWG-LRKLRKRLLR (mApoE), which is derived from the receptor binding sequence of apolipoprotein E, is effectively able to inhibit A&beta, aggregation and to promote fibril disaggregation. Taking advantage of Atomic Force Microscopy (AFM) imaging and fluorescence techniques, we investigate if the clustering of mApoE on gold nanoparticles (AuNP) surface may affect its performance in controlling A&beta, aggregation/disaggregation processes. The results showed that the ability of free mApoE to destroy preformed A&beta, fibrils or to hinder the A&beta, aggregation process is preserved after its clustering on AuNP. This allows the possibility to design multifunctional drug delivery systems with clustering of anti-amyloidogenic molecules on any NP surface without affecting their performance in controlling A&beta, aggregation processes.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. In ALS mice, neurodegeneration is associated with the proliferative restorative attempts of ependymal stem progenitor cells (epSPCs) that normally lie in a quiescent in the spinal cord. Thus, modulation of the proliferation of epSPCs may represent a potential strategy to counteract neurodegeneration. Recent studies demonstrated that FM19G11, a hypoxia-inducible factor modulator, induces epSPC self-renewal and proliferation. The aim of the study was to investigate whether FM19G11-loaded gold nanoparticles (NPs) can affect self-renewal and proliferation processes in epSPCs isolated from G93A-SOD1 mice at disease onset. We discovered elevated levels of SOX2, OCT4, AKT1, and AKT3, key genes associated with pluripotency, self-renewal, and proliferation, in G93A-SOD1 epSPCs at the transcriptional and protein levels after treatment with FM19G11-loaded NPs. We also observed an increase in the levels of the mitochondrial uncoupling protein (UCP) gene in treated cells. FM19G11-loaded NPs treatment also affected the expression of the cell cycle-related microRNA (miR)-19a, along with its target gene PTEN, in G93A-SOD1 epSPCs. Overall our findings establish the significant impact of FM19G11-loaded NPs on the cellular pathways involved in self-renewal and proliferation in G93A-SOD1 epSPCs, thus providing an impetus to the design of novel tailored approaches to delay ALS disease progression.

Engineered nanoparticles offer the chance to improve drug transport and delivery through biological barriers, exploiting the possibility to leave the blood circulation and traverse the endothelial vascular bed, blood-brain barrier (BBB) included, to reach their target. It is known that nanoparticles gather molecules on their surface upon contact with biological fluids, forming the "protein corona", which can affect their fate and therapeutic/diagnostic performance, yet no information on the corona's evolution across the barrier has been gathered so far. Using a cellular model of the BBB and gold nanoparticles, we show that the composition of the corona undergoes dramatic quantitative and qualitative molecular modifications during passage from the "blood" to the "brain" side, while it is stable once beyond the BBB. Thus, we demonstrate that the nanoparticle corona dynamically and drastically evolves upon crossing the BBB and that its initial composition is not predictive of nanoparticle fate and performance once beyond the barrier at the target organ.

Gold nanoparticles coated with fluorinated ligands (F-MPCs) present features suitable for (19)F MRI as observed from phantom experiments. Cellular uptake, by HeLa cells, and toxicity of fluorescent dye-decorated F-MPCs are presented together with their ability to bind hydrophobic molecules allowing for a potential combination of targeting, delivery and imaging features.