Neopterin as a potential prognostic and predictive biomarker in metastatic renal cell carcinoma treated with immune checkpoint inhibitors.

INTRODUCTION: Immunotherapy represents a significant and essential component of renal carcinoma therapy (RCC), but the selection of an optimal regimen for an individual patient remains unclear. Despite significant improvements in therapeutic options for RCC, predictive biomarkers for immunotherapeutic agents remain elusive. Neopterin is a biomarker of cell-mediated immune response, with concentrations increased in different disorders, including cancer. High neopterin levels herald, in general, a poor prognosis. AREAS COVERED: This review briefly overviews the contemporary clinical data on biomarkers in metastatic RCC therapy, focusing on neopterin. EXPERT OPINION: Elevated neopterin levels have been observed in tumors of different primary locations. Research indicates that neopterin may serve as a potential biomarker for assessing the inflammatory status associated with certain cancers. However, it is necessary to interpret neopterin levels in the context of a comprehensive clinical evaluation, as elevated neopterin alone is not specific to cancer and can be influenced by other factors, including comorbid conditions. Neopterin has also been identified as a prognostic biomarker. An increasing neopterin level in serum and urine is associated with advanced cancer, but the role as a potential predictor of response to immunotherapy has yet to be established. A reliable biomarker for optimal therapy selection in metastatic RCC is still putative.

Retraction Note: Air-stable superparamagnetic metal nanoparticles entrapped in graphene oxide matrix.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1038/s41467-020-19968-3.

The environmental fate of graphene oxide in aquatic environment-Complete mitigation of its acute toxicity to planktonic and benthic crustaceans by algae.

Graphene oxide (GO) as the most studied hydrophilic graphene derivative can be deployed in a broad spectrum of environmental technologies opening the issue of its ecotoxicity. Nevertheless, the information about its behavior in complex aquatic environment is still not sufficient. Here, we studied the interaction of three differently oxidized GO systems with planktonic and benthic crustaceans. By standard toxicity tests, we observed the importance of feeding strategy as well as the surface oxidation of GO with respect to GO's ecotoxicity. However, to gain a clearer insight into GO's environmental fate, we introduced a pre-treatment with algae as the most common source of food for crustaceans. Such an adjustment mimicking the conditions in real aquatic ecosystems resulted in complete mitigation of acute toxicity of GOs to all organisms and, more importantly, to the eradication of oxidative stress caused by GOs. We argue, that the pre-exposition of food is a crucial factor in GO's overall environmental fate, even though this fact has been completely neglected in recent studies. These experiments proved that GO is not a hazardous material in complex aquatic environments because its acute toxicity can be successfully mitigated through the interaction with algae even at very high concentrations (25 mg/L).

A carbon dot-based tandem luminescent solar concentrator.

Luminescent solar concentrators (LSCs) are light-management devices and are used for harvesting and concentrating solar light from a large area to their edges. Being semitransparent devices, LSCs show great promise for future utilization in glass walls of urban buildings as environmentally friendly photovoltaic power plants. The development of cheap and eco-safe materials, the extension of the LSC operation range, and the enhancement of the optical efficiency are the key challenges, which need to be solved in order to transform energetically passive buildings into self-sustainable units. Herein, a large area (64 cm2) tandem LSC fabricated using entirely eco-friendly highly emissive blue, green, and red carbon dots is demonstrated, with an internal optical quantum efficiency of 23.6% and an external optical quantum efficiency of 2.3%, while maintaining a high transparency across the visible spectrum. This opens up a new direction for the application of carbon dots in advanced solar light harvesting technologies.

Author Correction: Air-stable superparamagnetic metal nanoparticles entrapped in graphene oxide matrix.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Zigzag sp2 Carbon Chains Passing through an sp3 Framework: A Driving Force toward Room-Temperature Ferromagnetic Graphene.

Stabilization of ferromagnetic ordering in graphene-based systems up to room temperature remains an important challenge owing to the huge scope for applications in electronics, spintronics, biomedicine, and separation technologies. To date, several strategies have been proposed, including edge engineering, introduction of defects and dopants, and covalent functionalization. However, these techniques are usually hampered by limited temperature sustainability of ferromagnetic ordering. Here, we describe a method for the well-controlled sp3 functionalization of graphene to synthesize zigzag conjugated sp2 carbon chains that can act as communication pathways among radical motifs. Zigzag sp2/sp3 patterns in the basal plane were clearly observed by high-resolution scanning transmission electron microscopy and provided a suitable matrix for stabilization of ferromagnetic ordering up to room temperature due to combined contributions of itinerant π-electrons and superexchange interactions. The results highlight the principal role of sp2/sp3 ratio and superorganization of radical motifs in graphene for generating room-temperature nonmetallic magnets.

In vivo theranostics with near-infrared-emitting carbon dots-highly efficient photothermal therapy based on passive targeting after intravenous administration.

Carbon dots that exhibit near-infrared fluorescence (NIR CDs) are considered emerging nanomaterials for advanced biomedical applications with low toxicity and superior photostability and targeting compared to currently used photoluminescence agents. Despite progress in the synthesis of NIR CDs, there remains a key obstacle to using them as an in vivo theranostic agent. This work demonstrates that the newly developed sulfur and nitrogen codoped NIR CDs are highly efficient in photothermal therapy (PTT) in mouse models (conversion efficiency of 59%) and can be readily visualized by photoluminescence and photoacoustic imaging. The real theranostic potential of NIR CDs is enhanced by their unique biodistribution and targeting. Contrary to all other nanomaterials that have been tested in biomedicine, they are excreted through the body's renal filtration system. Moreover, after intravenous injection, NIR CDs are accumulated in tumor tissue via passive targeting, without any active species such as antibodies. Due to their accumulation in tumor tissue without the need for intratumor injection, high photothermal conversion, excellent optical and photoacoustic imaging performance, and renal excretion, the developed CDs are suitable for transfer to clinical biomedical practice.

Graphitic Nitrogen Triggers Red Fluorescence in Carbon Dots.

Carbon dots (CDs) are a stable and highly biocompatible fluorescent material offering great application potential in cell labeling, optical imaging, LED diodes, and optoelectronic technologies. Because their emission wavelengths provide the best tissue penetration, red-emitting CDs are of particular interest for applications in biomedical technologies. Current synthetic strategies enabling red-shifted emission include increasing the CD particle size (sp2 domain) by a proper synthetic strategy and tuning the surface chemistry of CDs with suitable functional groups (e.g., carboxyl). Here we present an elegant route for preparing full-color CDs with well-controllable fluorescence at blue, green, yellow, or red wavelengths. The two-step procedure involves the synthesis of a full-color-emitting mixture of CDs from citric acid and urea in formamide followed by separation of the individual fluorescent fractions by column chromatography based on differences in CD charge. Red-emitting CDs, which had the most negative charge, were separated as the last fraction. The trend in the separation, surface charge, and red-shift of photoluminescence was caused by increasing amount of graphitic nitrogen in the CD structure, as was clearly proved by XPS, FT-IR, Raman spectroscopy, and DFT calculations. Importantly, graphitic nitrogen generates midgap states within the HOMO-LUMO gap of the undoped systems, resulting in significantly red-shifted light absorption that in turn gives rise to fluorescence at the low-energy end of the visible spectrum. The presented findings identify graphitic nitrogen as another crucial factor that can red-shift the CD photoluminescence.

DOTA analogues with a phosphinate-iminodiacetate pendant arm: modification of the complex formation rate with a strongly chelating pendant.

The new ligand H6do3aPida combines the macrocyclic DOTA-like cavity and the open-chain iminodiacetate group connected through a coordinating phosphinate spacer. Its acid-base and coordination properties in solution were studied by potentiometry. Thermodynamic coordination characteristics of both chelating units are similar to those reported for H4dota and iminodiacetic acid themselves, respectively, so, macrocyclic and iminodiacetate units behave independently. The formation kinetics of the Ce(iii)-H6do3aPida complex was studied by UV-Vis spectrophotometry. Various out-of-cage intermediates were identified with 1 : 1, 1 : 2 and 2 : 1 ligand-to-metal ratios. The presence of the strongly coordinating iminodiacetate group significantly slows down the metal ion transfer into the macrocyclic cavity and, so, the formation of the in-cage complex is two orders of magnitude slower than that reported for the Ce(iii)-H4dota system. The kinetic inertness of the [Ce(do3aPida)]3- complex towards acid-assisted dissociation is comparable to that of the [Ce(dota)]- complex. The coordination modes of the ligand are demonstrated in the solid-state structure of [Cu4(do3aPida)(OH)(H2O)4]Cl·7.5H2O.

Room temperature organic magnets derived from sp3 functionalized graphene.

Materials based on metallic elements that have d orbitals and exhibit room temperature magnetism have been known for centuries and applied in a huge range of technologies. Development of room temperature carbon magnets containing exclusively sp orbitals is viewed as great challenge in chemistry, physics, spintronics and materials science. Here we describe a series of room temperature organic magnets prepared by a simple and controllable route based on the substitution of fluorine atoms in fluorographene with hydroxyl groups. Depending on the chemical composition (an F/OH ratio) and sp3 coverage, these new graphene derivatives show room temperature antiferromagnetic ordering, which has never been observed for any sp-based materials. Such 2D magnets undergo a transition to a ferromagnetic state at low temperatures, showing an extraordinarily high magnetic moment. The developed theoretical model addresses the origin of the room temperature magnetism in terms of sp2-conjugated diradical motifs embedded in an sp3 matrix and superexchange interactions via -OH functionalization.

Air-stable superparamagnetic metal nanoparticles entrapped in graphene oxide matrix.

Superparamagnetism is a phenomenon caused by quantum effects in magnetic nanomaterials. Zero-valent metals with diameters below 5 nm have been suggested as superior alternatives to superparamagnetic metal oxides, having greater superspin magnitudes and lower levels of magnetic disorder. However, synthesis of such nanometals has been hindered by their chemical instability. Here we present a method for preparing air-stable superparamagnetic iron nanoparticles trapped between thermally reduced graphene oxide nanosheets and exhibiting ring-like or core-shell morphologies depending on iron concentration. Importantly, these hybrids show superparamagnetism at room temperature and retain it even at 5 K. The corrected saturation magnetization of 185 Am(2) kg(-1) is among the highest values reported for iron-based superparamagnets. The synthetic concept is generalized exploiting functional groups of graphene oxide to stabilize and entrap cobalt, nickel and gold nanoparticles, potentially opening doors for targeted delivery, magnetic separation and imaging applications.

Targeted Drug Delivery with Polymers and Magnetic Nanoparticles: Covalent and Noncovalent Approaches, Release Control, and Clinical Studies.

Targeted delivery combined with controlled drug release has a pivotal role in the future of personalized medicine. This review covers the principles, advantages, and drawbacks of passive and active targeting based on various polymer and magnetic iron oxide nanoparticle carriers with drug attached by both covalent and noncovalent pathways. Attention is devoted to the tailored conjugation of targeting ligands (e.g., enzymes, antibodies, peptides) to drug carrier systems. Similarly, the approaches toward controlled drug release are discussed. Various polymer-drug conjugates based, for example, on polyethylene glycol (PEG), N-(2-hydroxypropyl)methacrylamide (HPMA), polymeric micelles, and nanoparticle carriers are explored with respect to absorption, distribution, metabolism, and excretion (ADME scheme) of administrated drug. Design and structure of superparamagnetic iron oxide nanoparticles (SPION) and condensed magnetic clusters are classified according to the mechanism of noncovalent drug loading involving hydrophobic and electrostatic interactions, coordination chemistry, and encapsulation in porous materials. Principles of covalent conjugation of drugs with SPIONs including thermo- and pH-degradable bonds, amide linkage, redox-cleavable bonds, and enzymatically-cleavable bonds are also thoroughly described. Finally, results of clinical trials obtained with polymeric and magnetic carriers are analyzed highlighting the potential advantages and future directions in targeted anticancer therapy.

Dichlorocarbene-Functionalized Fluorographene: Synthesis and Reaction Mechanism.

Halogen functionalization of graphene is an important branch of graphene research as it provides opportunities to tailor the band gap and catalytic properties of graphene. Monovalent C-X bond obviates pitfalls of functionalization with atoms of groups 13, 15, and 16, which can introduce various poorly defined groups. Here, the preparation of functionalized graphene containing both fluorine and chlorine atoms is shown. The starting material, fluorographite, undergoes a reaction with dichlorocarbene to provide dichlorocarbene-functionalized fluorographene (DCC-FG). The material is characterized by X-ray photoelectron spectroscopy, Raman spectroscopy, and high-resolution transmission electron microscopy with X-ray dispersive spectroscopy. It is found that the chlorine atoms in DCC-FG are distributed homogeneously over the entire area of the fluorographene sheet. Further density functional theory calculations show that the mechanism of dichlorocarbene attack on fluorographene sheet is a two-step process. Dichlorocarbene detaches fluorine atoms from fluorographene sheet and subsequently adds to the newly formed sp(2) carbons. Halogenated graphene consisting of two (or eventually three) types of halogen atoms is envisioned to find its way as new graphene materials with tailored properties.

Thiofluorographene-hydrophilic graphene derivative with semiconducting and genosensing properties.

We present the first example of covalent chemistry on fluorographene, enabling the attachment of -SH groups through nucleophilic substitution of fluorine in a polar solvent. The resulting thiographene-like, 2D derivative is hydrophilic with semiconducting properties and bandgap between 1 and 2 eV depending on F/SH ratio. Thiofluorographene is applied in DNA biosensing by electrochemical impedance spectroscopy.

Tailored functionalization of iron oxide nanoparticles for MRI, drug delivery, magnetic separation and immobilization of biosubstances.

In this critical review, we outline various covalent and non-covalent approaches for the functionalization of iron oxide nanoparticles (IONPs). Tuning the surface chemistry and design of magnetic nanoparticles are described in relation to their applicability in advanced medical technologies and biotechnologies including magnetic resonance imaging (MRI) contrast agents, targeted drug delivery, magnetic separations and immobilizations of proteins, enzymes, antibodies, targeting agents and other biosubstances. We review synthetic strategies for the controlled preparation of IONPs modified with frequently used functional groups including amine, carboxyl and hydroxyl groups as well as the preparation of IONPs functionalized with other species, e.g., epoxy, thiol, alkane, azide, and alkyne groups. Three main coupling strategies for linking IONPs with active agents are presented: (i) chemical modification of amine groups on the surface of IONPs, (ii) chemical modification of bioactive substances (e.g. with fluorescent dyes), and (iii) the activation of carboxyl groups mainly for enzyme immobilization. Applications for drug delivery using click chemistry linking or biodegradable bonds are compared to non-covalent methods based on polymer modified condensed magnetic nanoclusters. Among many challenges, we highlight the specific surface engineering allowing both therapeutic and diagnostic applications (theranostics) of IONPs and magnetic/metallic hybrid nanostructures possessing a huge potential in biocatalysis, green chemistry, magnetic bioseparations and bioimaging.

A magnetically drivable nanovehicle for curcumin with antioxidant capacity and MRI relaxation properties.

Curcumin possesses wide-ranging anti-inflammatory and anti-cancer properties and its biological activity can be linked to its potent antioxidant capacity. Superparamagnetic maghemite (γ-Fe2 O3 ), called surface-active maghemite nanoparticles (SAMNs) were surface-modified with curcumin molecules, due to the presence of under-coordinated Fe(III) atoms on the nanoparticle surface. The so-obtained curcumin-modified SAMNs (SAMN@curcumin) had a mean size of 13±4 nm. SAMN@curcumin was characterized by transmission and scanning electron microscopy, UV/Vis, FTIR, and Mössbauer spectroscopy, X-ray powder diffraction, bulk susceptibility (SQUID), and relaxometry measurements (MRI imaging). The high negative contrast proclivity of SAMN@curcumin to act as potential contrast agent in MRI screenings was also tested. Moreover, the redox properties of bound curcumin were probed by electrochemistry. SAMN@curcumin was studied in the presence of different electroactive molecules, namely hydroquinone, NADH and ferrocyanide, to assess its redox behavior. Finally, SAMN@curcumin was electrochemically probed in the presence of hydrogen peroxide, demonstrating the stability and reactivity of bound curcumin.