The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.
Here we have investigated the effect of enshrouding polymer-coated nanoparticles (NPs) with polyethylene glycol (PEG) on the adsorption of proteins and uptake by cultured cells. PEG was covalently linked to the polymer surface to the maximal grafting density achievable under our experimental conditions. Changes in the effective hydrodynamic radius of the NPs upon adsorption of human serum albumin (HSA) and fibrinogen (FIB) were measured in situ using fluorescence correlation spectroscopy. For NPs without a PEG shell, a thickness increase of around 3 nm, corresponding to HSA monolayer adsorption, was measured at high HSA concentration. Only 50% of this value was found for NPs with PEGylated surfaces. While the size increase clearly reveals formation of a protein corona also for PEGylated NPs, fluorescence lifetime measurements and quenching experiments suggest that the adsorbed HSA molecules are buried within the PEG shell. For FIB adsorption onto PEGylated NPs, even less change in NP diameter was observed. In vitro uptake of the NPs by 3T3 fibroblasts was reduced to around 10% upon PEGylation with PEG chains of 10 kDa. Thus, even though the PEG coatings did not completely prevent protein adsorption, the PEGylated NPs still displayed a pronounced reduction of cellular uptake with respect to bare NPs, which is to be expected if the adsorbed proteins are not exposed on the NP surface.
We report a procedure to prepare highly monodisperse copper telluride nanocubes, nanoplates, and nanorods. The procedure is based on the reaction of a copper salt with trioctylphosphine telluride in the presence of lithium bis(trimethylsilyl)amide and oleylamine. CuTe nanocrystals display a strong near-infrared optical absorption associated with localized surface plasmon resonances. We exploit this plasmon resonance for the design of surface-enhanced Raman scattering sensors for unconventional optical probes. Furthermore, we also report here our preliminary analysis of the use of CuTe nanocrystals as cytotoxic and photothermal agents.
Nanomaterials offer opportunities to construct novel compounds for many different fields. Applications include devices for energy, including solar cells, batteries, and fuel cells, and for health, including contrast agents and mediators for photodynamic therapy and hyperthermia. Despite these promising applications, any new class of materials also bears a potential risk for human health and the environment. The advantages and innovations of these materials must be thoroughly compared against risks to evaluate each new nanomaterial. Although nanomaterials are often used intentionally, they can also be released unintentionally either inside the human body, through wearing of a prosthesis or the inhalation of fumes, or into the environment, through mechanical wear or chemical powder waste. This possibility adds to the importance of understanding potential risks from these materials. Because of fundamental differences in nanomaterials, sound risk assessment currently requires that researchers perform toxicology studies on each new nanomaterial. However, if toxicity could be correlated to the basic physicochemical properties of nanomaterials, those relationships could allow researchers to predict potential risks and design nanomaterials with minimum toxicity. In this Account we describe the physicochemical properties of nanoparticles (NPs) and how they can be determined and discuss their general importance for cytotoxicity. For simplicity, we focus primarily on in vitro toxicology that examines the interaction of living cells with engineered colloidal NPs with an inorganic core. Serious risk assessment of NPs will require additional in vivo studies. Basic physicochemical properties of nanoparticulate materials include colloidal stability, purity, inertness, size, shape, charge, and their ability to adsorb environmental compounds such as proteins. Unfortunately, the correlation of these properties with toxicity is not straightforward. First, for NPs released either unintentionally or intentionally, it can be difficult to pinpoint these properties in the materials. Therefore, researchers typically use NP models with better defined properties, which don't include the full complexity of most industrially relevant materials. In addition, many of these properties are strongly mutually connected. Therefore, it can be difficult to vary individual properties in NP models while keeping the others constant.
The protein adsorption layer (a.k.a. the "protein corona") that forms on the surface of colloidal nanoparticles plays an important role in their interaction with living matter. Thus, characterization of the protein corona is of utmost importance for understanding how exposure to nanoparticles affects the biological responses of cells and organisms. Although a lot of experimental studies have been reported in this direction, a comprehensive picture is still missing, in particular due to the multitude of different scenarios under which experiments have been performed. In this review an analysis of existing experimental data about the protein corona, and an outline for required future work will be given. In particular we review how existing simple analytical models such as the adopted Hill model may help to extract quantitative data from such experiments such as equilibrium dissociation and kinetic coefficients. Careful quantitative assessment of equilibrium and kinetic properties would allow for a comparison of protein binding data from the vast array of engineered nanoparticles, so that basic principles could be revealed. This review outlines that the field is in dire need of more quantitative studies to further our understanding of protein corona formation and its biological consequences. Development of new materials demands consistent characterization techniquesThe development of new materials always goes hand-in-hand with their characterization. A wide variety of analytical techniques exist that allow materials properties to be assessed in a quantitative fashion. Still, the results oen depend on a range of experimental parameters. If these are being varied from experiment to
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