Removal of Circulating Tumor Cells from Blood Samples of Cancer Patients Using Highly Magnetic Nanoparticles: A Translational Research Project.

The count of circulating tumor cells (CTCs) has been associated with a worse prognosis in different types of cancer. Perioperatively, CTCs detach due to mechanical forces. Diagnostic tools exist to detect and isolate CTCs, but no therapeutic technique is currently available to remove CTCs in vivo from unprocessed blood. The aim of this study was to design and test new magnetic nanoparticles to purify whole blood from CTCs. Novel magnetic carbon-coated cobalt (C/Co) nanoparticles conjugated with anti-epithelial cell adhesion molecule (EpCAM) antibodies were synthesized, and their antifouling and separation properties were determined. The newly developed C/Co nanoparticles showed excellent separation and antifouling properties. They efficiently removed tumor cells that were added to healthy subjects' blood samples, through an anti-EpCAM antibody interaction. The nanoparticles did not interact with other blood components, such as lymphocytes or the coagulation system. In blood samples of carcinoma patients suffering from metastatic disease, on average, ≥68% of CTCs were removed. These nanoparticles could prompt the development of a blood purification technology, such as a dialysis-like device, to perioperatively remove CTCs from the blood of cancer patients in vivo and potentially improve their prognosis.

Water dispersible surface-functionalized platinum/carbon nanorattles for size-selective catalysis.

Selective dealloying of metal nanoparticles results in rattle-type hollow carbon nanoshells enclosing platinum nanoparticles, which are able to perform size-selective catalysis. Selective functionalization of the outer graphene-like carbon surface prevents agglomeration and leads to well dispersible nanocatalysts in aqueous solutions. The synthesis starts with the production of nanoparticles with a cobalt-platinum-alloy core surrounded by graphene-like carbon via reducing flame spray synthesis. After surface functionalization, simultaneous pore formation in the shell-wall and dissolution of the cobalt results in platinum encapsulated in hollow carbon nanospheres. Catalytic oxidation of differently sized sugars (glucose and maltoheptaose) reveales size-selective catalytic properties of these platinum nanorattles.

Facile meltPEGylation of flame-made luminescent Tb3+-doped yttrium oxide particles: hemocompatibility, cellular uptake and comparison to silica.

Flame aerosol technology is a versatile method for scalable synthesis of nanoparticles. Since particles are produced and collected in a dry state, dispersibility and further functionalization could pose hurdles to their biomedical use. We report on a one-pot, scalable and robust procedure for the PEGylation of flame-made yttria and silica nanoparticles. We demonstrate improved colloidal stability, attenuated activation of blood coagulation and decreased uptake into phagocytic cells, all of which pave the way for facilitated biomedical use of flame-made oxide nanoparticles.

Nondestructive in-line sub-picomolar detection of magnetic nanoparticles in flowing complex fluids.

Over the last decades, the use of magnetic nanoparticles in research and commercial applications has increased dramatically. However, direct detection of trace quantities remains a challenge in terms of equipment cost, operating conditions and data acquisition times, especially in flowing conditions within complex media. Here we present the in-line, non-destructive detection of magnetic nanoparticles using high performance atomic magnetometers at ambient conditions in flowing media. We achieve sub-picomolar sensitivities measuring ~30 nm ferromagnetic iron and cobalt nanoparticles that are suitable for biomedical and industrial applications, under flowing conditions in water and whole blood. Additionally, we demonstrate real-time surveillance of the magnetic separation of nanoparticles from water and whole blood. Overall our system has the merit of in-line direct measurement of trace quantities of ferromagnetic nanoparticles with so far unreached sensitivities and could be applied in the biomedical field (diagnostics and therapeutics) but also in the industrial sector.

Protein Reduction and Dialysis-Free Work-Up through Phosphines Immobilized on a Magnetic Support: TCEP-Functionalized Carbon-Coated Cobalt Nanoparticles.

Tris(2-carboxyethyl)phosphine (TCEP) is an often-used reducing agent in biochemistry owing to its selectivity towards disulfide bonds. As TCEP causes undesired consecutive side reactions in various analytical methods (e.g., gel electrophoresis, protein labeling), it is usually removed by means of dialysis or gel filtration. Here, an alternative method of separation is presented, namely the immobilization of TCEP on magnetic nanoparticles. This magnetic reagent provides a simple and rapid approach to remove the reducing agent after successful reduction. A reduction capacity of 70 µmol per gram of particles was achieved by using surface-initiated atom transfer polymerization.

Hollow Carbon Nanobubbles: Synthesis, Chemical Functionalization, and Container-Type Behavior in Water.

Thin-walled, hollow carbon nanospheres with a hydrophobic interior and good water dispersability can be synthesized in two steps: First, metal nanoparticles, coated with a few layers of graphene-like carbon, are selectively modified on the outside with a covalently attached hydrophilic polymer. Second, the metal core is removed at elevated temperature treatment with acid, leaving a well-defined carbon-based hydrophobic cavity. Loading experiments with the dye rhodamine B and doxorubicin confirmed the filling and release of a cargo and adjustment of a dynamic equilibrium (cargo-loaded versus release). Rhodamine B preferably accumulates in the interior of the bubbles. Filled nanobubbles allowed constant dye release into pure water. Studies of the concentration-dependent loading and release show an unusual hysteresis.

Click and release: fluoride cleavable linker for mild bioorthogonal separation.

Herein, we present a water dispersable, magnetic nanoparticle supported "click and release" system. The cleavable linker has been synthesized by using a strain-promoted copper-free "click" reagent to establish the specific link and a fluoride cleavable silane moiety for mild cleavage. Small organic molecules, azide-bearing dyes and functionalized enzymes have been bound to the magnetic particle and released in a bioorthogonal way.

Porous, Water-Resistant Multifilament Yarn Spun from Gelatin.

Sustainability, renewability, and biodegradability of polymeric material constantly gain in importance. A plausible approach is the recycling of agricultural waste proteins such as keratin, wheat gluten, casein or gelatin. The latter is abundantly available from animal byproducts and may well serve as building block for novel polymeric products. In this work, a procedure for the dry-wet spinning of multifilament gelatin yarns was developed. The process stands out as precipitated gelatin from a ternary mixture (gelatin/solvent/nonsolvent) was spun into porous filaments. About 1000 filaments were twisted into 2-ply yarns with good tenacity (4.7 cN tex(-1)). The gelatin yarns, per se susceptible to water, were cross-linked by different polyfunctional epoxides and examined in terms of free lysyl amino groups and swelling degree in water. Ethylene glycol diglycidyl ether exhibited the highest cross-linking efficiency. Further post-treatments with gaseous formaldehyde and wool grease (lanolin) rendered the gelatin yarns water-resistant, allowing for multiple swelling cycles in water or in detergent solution. However, the swelling caused a decrease in filament porosity from ∼30% to just below 10%. To demonstrate the applicability of gelatin yarn in a consumer good, a gelatin glove with good thermal insulation capacity was fabricated.

Adsorption and separation of amyloid beta aggregates using ferromagnetic nanoparticles coated with charged polymer brushes.

Amyloid beta (Aß) protein aggregates, which include fibrils and oligomers, are neurotoxic and are considered to cause Alzheimer's disease. Thus, separation of these Aß aggregates from biological samples is important. Herein, we report the use of strongly ferromagnetic few-layer graphene-coated magnetic nanoparticles (C/Co), which were functionalized with a cationic polymer, poly[3-(methacryloyl amino)propyl]trimethylammonium chloride (polyMAPTAC), C/Co@polyMAPTAC, for the adsorption and magnetic separation of Aß aggregates. Fast adsorption (∼1 min) of Aß fibrils and oligomers onto the particles was observed. Interestingly, the Aß monomer was not captured by the particles, suggesting that binding to Aß molecules is toxic species-selective. Selective adsorption was also observed in the presence of serum albumin protein. We also showed that C/Co@polyMAPTAC could reduce the cytotoxicity of the Aß aggregate solutions. This study should be useful for further elucidation of the application of nanoparticle adsorption in mediating Aß toxicity.

Magnetic superbasic proton sponges are readily removed and permit direct product isolation.

Workup in organic synthesis can be very time-consuming, particularly when using reagents with both a solubility similar to that of the desired products and a tendency not to crystallize. In this respect, reactions involving organic bases would strongly benefit from a tremendously simplified separation process. Therefore, we synthesized a derivative of the superbasic proton sponge 1,8-bis(dimethylamino)naphthalene (DMAN) and covalently linked it to the strongest currently available nanomagnets based on carbon-coated cobalt metal nanoparticles. The immobilized magnetic superbase reagent was tested in Knoevenagel- and Claisen-Schmidt-type condensations and showed conversions of up to 99%. High yields of up to 97% isolated product could be obtained by simple recrystallization without using column chromatography. Recycling the catalyst was simple and fast with an insignificant decrease in catalytic activity.

Efficient magnetic recycling of covalently attached enzymes on carbon-coated metallic nanomagnets.

In the pursuit of robust and reusable biocatalysts for industrial synthetic chemistry, nanobiotechnology is currently taking a significant part. Recently, enzymes have been immobilized on different nanoscaffold supports. Carbon coated metallic nanoparticles were found to be a practically useful support for enzyme immobilization due to their large surface area, high magnetic saturation, and manipulatable surface chemistry. In this study carbon coated cobalt nanoparticles were chemically functionalized (diazonium chemistry), activated for bioconjugation (N,N-disuccinimidyl carbonate), and subsequently used in enzyme immobilization. Three enzymes, ß-glucosidase, α-chymotrypsin, and lipase B were successfully covalently immobilized on the magnetic nonsupport. The enzyme-particle conjugates formed retained their activity and stability after immobilization and were efficiently recycled from milliliter to liter scales in short recycle times.

Synthesis of trisubstituted ureas by a multistep sequence utilizing recyclable magnetic reagents and scavengers.

Unprecedented magnetic borohydride exchange (mBER), magnetic Wang aldehyde (mWang) and magnetic amine resins were prepared from highly magnetic polymer-coated cobalt or iron nanoparticles. Microwave irradiation was used to obtain excellent degrees of functionalization (>95 %) and loadings (up to 3.0 mmol g(-1)) in short reaction times of 15 min or less. A small library of ureas and thioureas was synthesized by the exclusive application of these magnetic resins. As a first step, a reductive amination of aromatic and aliphatic aldehydes was carried out with mBER. The excess of primary amine needed to complete the reaction was subsequently scavenged selectively by mWang. Simple magnetic decantation from the resins resulted in secondary amines in good to excellent yields and purities. The used magnetic resins were efficiently regenerated and reused for the next run. In a second step, the secondary amines were converted to trisubstituted (thio)ureas in excellent yields and purities by stirring with an excess of iso(thio)cyanate, which was scavenged by addition of the magnetic amine resin after completion of the reaction. The whole reaction sequence is carried out without any purification apart from magnetic decantation; moreover, conventional magnetic stirring can be used as opposed to the vortexing required for polystyrene resins.

Ferromagnetic inks facilitate large scale paper recycling and reduce bleach chemical consumption.

Deinking is a fundamental part of paper recycling. As the global paper consumption rises and exceeds even the annual paper production, recycling of this raw material is of high importance. Magnetic ink based on carbon coated magnetic nanoparticles enables an alternative approach to state of the art paper deinking. Magnetic deinking comprises three steps (preselection, washing, and magnetic separation of fibers). Preseparation of printed from nonprinted scraps of paper is feasible and reduces the paper mass which has to be fed into a deinking process. A consecutive washing process removes surficial magnetic ink that can be collected by application of a permanent magnet. Still, printed parts are subjected to a further continuous magnetic deinking step, where magnetic and nonmagnetic paper fibers can be separated. Magnetic deinking of a model print allows recovery of more than 80% of bright fibers without any harsh chemical treatment and the re-collection of more than 82% of magnetic ink.

Magnetic silyl scaffold enables efficient recycling of protecting groups.

A novel organic/inorganic hybrid material comprising carboncoated cobalt nanoparticles and a poly(benzylchloride)styrene shell is the first magnetic support that complies with important requirements for immobilized reagents and scavengers, that is, stability under harsh conditions (e.g., acids), sufficient loading (up to 2 mmol g(-1)), and satisfying magnetization. The durability of the scaffold was demonstrated by immobilization of a trialkylsilane reagent, which served as a "magnetic" protecting group for a number of primary and secondary alcohols. Importantly, the scaffold could be efficiently separated, recycled, and reused after alcohol cleavage (HF·pyridine) via regeneration of the silyl chloride moiety with BCl(3).