Toward the boosted loading of cisplatin drug into liposome nanocarriers.

Current challenges in oncology are largely associated with the need to improve the effectiveness of cancer treatment and to reduce drug's side effects. An effective strategy to cope with these challenges is behind designing and developing drug delivery systems based on smart nanomaterials and approved anticancer drugs. The present study offers a novel and straightforward approach to efficiently load the cisplatin drug into the newly constructed liposome-based nanosystems as well a reliable technique for monitoring this process based on capillary electrophoresis hyphenated with inductively coupled plasma tandem mass spectrometry. The proposed drug-loading methodology comprises liposome formation via a simple ethanol-injection method and propels increased drug encapsulation using tailor-made freeze-thawing or lyophilization-hydration procedures. To optimize liposome generation and drug encapsulation, the effects of dilution medium and liposome composition (types of phospholipids and their percentage ratio) have been investigated in detail. It was shown that modest alterations of the composition of three-component phospholipid liposomes and parameters of the freeze-thawing procedure have a strong impact on the formation of cisplatin-liposome systems. The obtained cisplatin-liposome formulation features a remarkable degree of drug encapsulation, over 100 mg L-1, and holds promise for further preclinical development as a potent drug-delivery platform.

Nanoscale Ion-Exchange Materials: From Analytical Chemistry to Industrial and Biomedical Applications.

Nano-sized ion exchangers (NIEs) combine the properties of common bulk ion-exchange polymers with the unique advantages of downsizing into nanoparticulate matter. In particular, being by nature milti-charged ions exchangers, NIEs possess high reactivity and stability in suspensions. This brief review provides an introduction to the emerging landscape of various NIE materials and summarizes their actual and potential applications. Special attention is paid to the different methods of NIE fabrication and studying their ion-exchange behavior. Critically discussed are different examples of using NIEs in chemical analysis, e.g., as solid-phase extraction materials, ion chromatography separating phases, modifiers for capillary electrophoresis, etc., and in industry (fuel cells, catalysis, water softening). Also brought into focus is the potential of NIEs for controlled drug and contrast agent delivery.

Enhanced edible plant production using nano-manganese and nano-iron fertilizers: Current status, detection methods and risk assessment.

BACKGROUND: Nanotechnology offers many benefits in the globally important field of food production and human nutrition, particularly by implementing agricultural nanoproducts. Of these, edible plant fertilizers enriched with nanosized forms of essential metals, Mn and Fe, are growing in importance with the advantages of enhanced action on plant roots. SCOPE AND APPROACH: This review focuses on the importance of tracking the bioaccumulation and biodistribution of these pertinent nanofertilizers. An emphasis is given to the critical analysis of the state-of-the-art analytical strategies to examine the Mn and Fe nanoparticles in edible plant systems as well as to shedding light on the vast gap in the methodologies dedicated to the speciation, in vitro simulation, and safety testing of these promising nanomaterials. Also provided are guidances for the food chemists and technologists on the lights and shadows of particular analytical approaches as a matter of authors' expertise as analytical chemists. KEY FINDINGS AND CONCLUSIONS: While the use of nanotechnology in agriculture seems to be growing increasingly, there is still a lack of analytical methodologies capable of investigating novel Mn- and Fe-based nanomaterials as potential fertilizers. Only the advent of reliable analytical tools in the field could bridge the gaps in our knowledge about processes in which those materials participate in the plant systems and their effects on crop production and quality of the produced food.

Mass Spectrometry Insight for Assessing the Destiny of Plastics in Seawater.

Plastic pollution has become an increasingly serious environmental issue that requires using reliable analytical tools to unravel the transformations of primary plastics exposed to the marine environment. Here, we evaluated the performance of the isotope ratio mass spectrometry (IRMS) technique for identifying the origin of polymer material contaminating seawater and monitoring the compositional alterations due to its chemical degradation. Of twenty-six plastic specimens available as consumer products or collected from the Mediterranean Sea, five plastics were shown to originate from biobased polymeric materials. Natural abundance carbon and hydrogen isotope measurements revealed that biopolymers incline to substantial chemical transformation upon a prolonged exposure to seawater and sunlight irradiation. To assess the seawater-mediated aging that leads to the release of micro/nano fragments from plastic products, we propose to use microfiltration. Using this non-destructive separation technique as a front end to IRMS, the fragmentation of plastics (at the level of up to 0.5% of the total mass for plant-derived polymers) was recorded after a 3-month exposure and the rate and extent of disintegration were found to be substantially different for the different classes of polymers. Another potential impact of plastics on the environment is that toxic metals are adsorbed on their surface from the seashore water. We addressed this issue by using inductively coupled mass spectrometry after nitric acid leaching and found that several metals occur in the range of 0.1-90 µg per g on naturally aged plastics and accumulate at even higher levels (up to 10 mg g-1) on pristine plastics laboratory-aged in contaminated seawater. This study measured the degradation degree of different polymer types in seawater, filling in the gaps in our knowledge about plastic pollution and providing a useful methodology and important reference data for future research.

Analysis of Engineered Nanoparticles in Seawater Using ICP-MS-Based Technology: From Negative to Positive Samples.

A growing global emission of engineered nanoparticles (ENPs) into the aquatic environment has become an emerging safety concern that requires methods capable of identifying the occurrence and possibly determining the amounts of ENPs. In this study, we employed sector-field inductively coupled mass spectrometry to assess the presence of ENPs in coastal seawater samples collected from the Black Sea in regions suffering different anthropogenic impacts. Ultrafiltration through commercial 3 kDa membrane filters was shown to be feasible to separate the ENPs from the bulk seawater, and the subsequent ultrasound-mediated acidic dissolution makes the metals constituting the ENPs amenable to analysis. This procedure allowed the ENPs bearing Cu, Zn, V, Mo, and Sn to be for the first time quantitated in seashore surface water, their concentration ranging from 0.1 to 1.0 µg L-1 (as metal) and related to the presence of industry and/or urban stress. While these levels are decreased by natural dilution and possible sedimentation, the monitored ENPs remain measurable at a distance of 2 km from the coast. This can be attributed not only to local emission sources but also to some natural backgrounds.

Seawater analysis of engineered nanoparticles using ICP-MS-based technology: Addressing challenges with the development of reliable monitoring strategy.

With an increasing production and use of engineered nanoparticles (ENPs), inevitably grows their release into the environment. This makes it important to determine in what quantitates they occur in aquatic systems like seawater. However, even when using the most sensitive ICP-MS technique, quantification of very low seawater concentrations of ENPs is still concept rather than the fact. To approach this goal, a unified protocol for the preparation of seawater samples for ICP-MS analysis has been developed in this study using a selection of silver, titanium dioxide and zinc oxide nanoparticles. In order to minimize the risk of particle loss, the effect of sample pH was examined and it was found out that a moderate in-field acidification (to pH 7.5) ensures particle stability prior to analysis. Ultrafiltration through commercial 3 kDa membrane filters was shown feasible to separate the ENPs from the bulk seawater sample provided that the filter unit is pre-conditioned with 0.1 M copper nitrate to avoid ionic metal adsorption. The following ultrasound-mediated dissolution in 30% HNO3 directly in the filer unit and ultrafiltration makes the metals constituting the ENPs amenable to analysis. The latter was for the first time performed using high-resolution ICP-MS method validated according to the common EU standards. The limits of detection attained here were as low as 0.06, 0.09, and 17.5 µg L-1 for Ag, TiO2, and ZnO nanoparticles, respectively. Accuracy of the method was tested with uncontaminated open-sea water spiked with ENPs and recoveries were acceptable ranging from 85 to 110%.

Marine sediment analysis - A review of advanced approaches and practices focused on contaminants.

This review is aimed at critical analysis of current and emerging capabilities of analytical methods as employed for marine sediment analysis. An emphasis is given to the most reliable experimental strategies used to quantifying the various classes of contaminants and thus to acquiring analytical information that is relevant to assess the quality of sediments with regard to possible pollution of marine ecosystems. Advanced analytical methodology in use basically relies on the application of mass spectrometry to enable identification and quantification of hazardous chemical species, directly or after separation using the principles of gas and liquid chromatography. Also addressed are sample preparation techniques which - given the complexity of sediment matrices and the diverse and multiple nature of contaminants - are often a key for successful analysis. Among the trends in marine sediment analysis is an inclination to chemicals that are only recently recognized as emerging pollutants of very high concern, such as microplastics, pharmaceuticals and their metabolites.

Versatile analytical methodology for evaluation of drug-like properties of potentially multi-targeting anticancer metallodrugs.

Using inductively coupled plasma mass spectrometry (in combination with ultrafiltration) and microemulsion electrokinetic chromatography, the drug properties of two new, potentially multi-targeting Ru(III) and Pt(IV) compounds, containing biologically active ligands, were evaluated. The ruthenium complex with bexarotene was shown to bind to albumin faster than to transferrin and exhibits much the same (to albumin) binding profile in human serum. The Pt(IV)-lonidamine complex interacts with albumin relatively slowly but possesses high stability and lipophilicity (log P 1.62), which makes it possible the cellular uptake in a free (of proteins) form. Although both examined compounds display a moderate solubility (below 10-4 M), this stands compatible with their nanomolar cytotoxic activities. The Ru(III) compound, whose active moiety is a complexed anion, is deemed promising to be loaded on nanoscale anion-exchangers with the aim of controlled delivery.

Analytical methodology for developing nanomaterials designed for magnetically-guided delivery of platinum anticancer drugs.

Metallodrug delivery using magnetic nanomaterials is emerging as a tool for the treatment of cancer because of its potential of enhanced and controlled delivery to a specific site within the body, reduced side effects, and protection of drugs from the extracellular environment. In this brief review, we discuss recent progress in the development of iron oxide nanoparticles loaded with platinum anticancer drugs due to applying modern analytical techniques. Such techniques may vary depending on what step of manufacture and assessment of magnetic nanocarriers is in question, i.e., drug loading, payload stability, magnetic properties, drug release or the efficiency against different cancer cell lines. While focusing on a wider implementation of advanced analytical methodologies, we also critically contemplate how they help create more potent magnetic nanoformulations, resolve the current challenges with the use of magnetic nanomaterials in smart metallodrug delivery and thus accelerate their translation to human treatments.

Protein-Mediated Transformations of Superparamagnetic Nanoparticles Evidenced by Single-Particle Inductively Coupled Plasma Tandem Mass Spectrometry: A Disaggregation Phenomenon.

Progress toward translating superparamagnetic iron oxide nanoparticles (SPIONs) with specific diagnostic and therapeutic properties for clinical applications depends on developing and implementing appropriate methodologies that would allow in-depth characterizations of their behavior in a real biological environment. Herein, we report a versatile approach for studying interactions between SPIONs and proteins using single-particle inductively coupled plasma tandem mass spectrometry. By monitoring the changes in the size distribution upon exposure to human serum, the formation of stable protein corona is revealed, accompanied by particle disaggregation.

Current and emerging mass spectrometry methods for the preclinical development of metal-based drugs: a critical appraisal.

This Trends article highlights the multiple ways in which the state-of-the-art molecular mass spectrometry can support the preclinical development of novel metal-based anticancer drugs. Examples from the recent literature-beyond routine characterization applications-are presented to illustrate what analytical and experimental design challenges are to be addressed to facilitate the translation of promising drug candidates to clinical practice.

Magnetic nanoparticles for highly robust, facile and efficient loading of metal-based drugs.

Direct interaction between iron oxide nanoparticles (IONs), modified with polyethylene glycol and an ionic liquid, and activated cisplatin drug resulted in a fast and high drug loading (up to 0.17 mol of platinum per gram of iron), and the payload does not strongly affect the magnetic properties of IONs and resists protein adsorption in human serum environment. For another, developmental metal-based drug, tris(8-quinolinolato)gallium(III), binding to the IONs allowed for overcoming the disadvantages of low solubility and incompatibility with intravenous administration. The potential of IONs as a magnetic nanoformulation for smart drug delivery has been confirmed by the release of both metallodrugs under conditions relevant to cancer cytosol.

Metal-Specific Response of High-Resolution ICP-MS for Proteins Binding to Gold Nanoparticles in Human Serum.

Metalloproteins have many different functions such as storage and transport of proteins, enzymes, signal transduction proteins, etc. Herein, for a selection of gold nanoparticles differing in shape, size, charge, and surface modification, the binding behavior in human serum was assessed with respect to metal-containing proteins. Our results based on sector-field ICP-MS measurements and a simple calculation algorithm indicate the possible involvement of proteins, incorporating Cu and Fe, in the formation of the biomolecular layer around the particle surface. Given that such binding encompasses a substantial amount of copper and iron within the serum proteome (>50%) at a calculated nanoparticle dose, it may result in depleting their biological functions and should be taken into account when selecting lead candidates with an improved biocompatibility.

How Feasible is Direct Determination of Rare Earth Elements in Seawater by ICP-MS?

With the increasingly wide industrial use of rare earth elements (REEs), their release into marine systems makes it important to understand in what quantities they occur and to what geochemical processes they contribute, preferably using direct analytical methodology. In this study, analytical performance of high-resolution ICP-MS was assessed with regard to quantification of REEs in seawater without matrix separation and analyte preconcentration. With optimized sample dilution, precise and interference-free quantifications of most of the REEs in samples taken from Kara Sea were obtained, with an accuracy of 3 to 9% (against the independently asserted values), repeatability of 3 to 5%, and intermediate precision and reproducibility, averaging 4 and 11%, respectively. The method was further validated by using a certified reference material for nearshore seawater. However, the limits of detection obtained (0.04 - 0.38 ng L-1), while not significantly inferior to those obtained after sample enrichment, appear to be not low enough to analyze high salinity sea samples (over 30 parts per thousand) or open-ocean water samples, which require higher dilution factors or contain (much) lower REE concentrations, respectively. Therefore, it was concluded that the direct determination of REEs is only possible from samples with moderate salinity such as estuarine or shallow-sea water. In the latter case, the longitudinal REE profiling assayed by ICP-MS allowed us to assume that the export of the contaminated material from land areas into estuaries and then to the sea by rivers may substantially contribute to the seawater pool of REEs.

Toward a deeper and simpler understanding of serum protein-mediated transformations of magnetic nanoparticles by ICP-MS.

A great variety of magnetic nanomaterials are entering preclinical investigations with the objective to select the most promising candidates for diagnostic and therapeutic applications. For an analytical approach to be used as a high-throughput screening tool, simple and cost-efficient sample preparation protocol is a basiс prerequisite. Here, we demonstrate how the application of continuous magnetic field allows for quantitatively separating iron oxide magnetic nanoparticles from a mixture with human serum to facilitate monitoring of their biomolecular interactions with high-resolution inductively coupled plasma mass spectrometry. By measuring the signals of sulfur and metal isotopes, it is possible to monitor the formation of the protein corona and alterations in the concentrations of relevant metals due to binding of specific metalloproteins, respectively.

Current trends and challenges in analysis and characterization of engineered nanoparticles in seawater.

With the increasingly wide use of engineered nanoparticles (ENPs), their release into the environment makes it important to determine in what quantitates they occur in aquatic systems and to understand their fate therein. In particular, detection and quantification of ENPs in seawater is challenging and often requires analytical methods to perform close to the feasibility confines. This review is aimed at critical analysis of current and emerging capabilities of analytical methods as have been employed for the analysis and characterization of ENPs in seawater in the last decade. An emphasis is given to the most reliable experimental strategies focused on avoiding the high-salt matrix effect and isolation and enrichment of the nanoparticulate fraction prior to analysis. Advanced analytical methodology in use basically relies on the application of elemental mass spectrometry to determine various particle-core metals and its single-particle mode to characterize the seawater-mediated transformation of ENPs, including dissolution, aggregation, etc. On the other hand, common microscopy, light scattering or X-ray based techniques are not sensitive enough to acquire the transformation information from real seawater samples. Finally, attention is pinpointed upon an acute shortcoming of the current research which is in the overwhelming majority of cases restricted to samples spiked with ENPs and often at excessive concentration levels.

An ICP-MS-based assay for characterization of gold nanoparticles with potential biomedical use.

Most of potential diagnostic and therapeutic nanoparticles fail to reach clinical trials because assessment of their 'drug-like' properties is often overlooked during the discovery stage. This compromises the results of cell culture and animal experiments, making them insufficient to evaluate the lead candidates for testing on patients. In this study, we demonstrate the potential of high-resolution inductively coupled plasma mass spectrometry (ICP-MS) as a nanoparticle qualification tool. Using novel gold nanoparticles stabilized by N-heterocyclic carbenes as test nanoparticles, it was shown that important prerequisites for biomedical applications, such as resistance to the action of human serum milieu or reactivity toward serum biomolecules, can be reliably assessed by recording the signals of gold or sulfur isotopes. Implemented during the screening stage, the method would provide benefits in shortening timelines and reducing cost for selection and initial testing of medicinal nanoparticle candidates.

High-resolution ICP-MS approach for characterization of magnetic nanoparticles for biomedical applications.

The potential of iron oxide-based nanoparticles (IONs) as theranostic agents is believed to be in a great part due to non-invasive diagnosis and therapeutic applications. However, there is still a lack of well-recognized methodology to assess bioresistance, hypotoxicity, reactivity toward pertinent biomolecules, as well as an eventual dose of IONs as prerequisites for their clinical use. In this study, we demonstrate how application of high-resolution ICP-MS in combination with conventional ultrafiltration can address these important issues in a simple and high-throughput way. Based upon interference-free and sensitive measurements of iron and sulfur isotopes ensured by sector-field ICP-MS mode, the comparative testing of a series of novel IONs modified by PEG or PEG and an ionic liquid, was performed. Satisfactory stability (less than 1 % of soluble Fe), minor toxicity (by virtue of releasing a free iron) and transit into bioconjugates in human serum, different in speed, proved the prospective of the tested IONs for in-depth preclinical development.

How well can we characterize human serum transformations of magnetic nanoparticles?

This mini-review summarizes analytical methods in use to uncover biochemical transformations that magnetic nanoparticles (MNPs) are possibly undergoing while residing in human blood. Examples from the recent literature are presented to illustrate what analytical challenges are to be addressed to shed light on this important issue of biomedical application of MNPs.