Search

In the past, our research group was able to successfully remove circulating tumor cells with magnetic nanoparticles. While these cancer cells are typically present in low numbers, we hypothesized that magnetic nanoparticles, besides catching single cells, are also capable of eliminating a large number of tumor cells from the blood ex vivo. This approach was tested in a small pilot study in blood samples of patients suffering from chronic lymphocytic leukemia (CLL), a mature B-cell neoplasm. Cluster of differentiation (CD) 52 is a ubiquitously expressed surface antigen on mature lymphocytes. Alemtuzumab (MabCampath®) is a humanized, IgG1κ, monoclonal antibody directed against CD52, which was formerly clinically approved for treating chronic lymphocytic leukemia (CLL) and therefore regarded as an ideal candidate for further tests to develop new treatment options. Alemtuzumab was bound onto carbon-coated cobalt nanoparticles. The particles were added to blood samples of CLL patients and finally removed, ideally with bound B lymphocytes, using a magnetic column. Flow cytometry quantified lymphocyte counts before, after the first, and after the second flow across the column. A mixed effects analysis was performed to evaluate removal efficiency. p < 0.05 was defined as significant. In the first patient cohort (n = 10), using a fixed nanoparticle concentration, CD19-positive B lymphocytes were reduced by 38% and by 53% after the first and the second purification steps (p = 0.002 and p = 0.005), respectively. In a second patient cohort (n = 11), the nanoparticle concentration was increased, and CD19-positive B lymphocytes were reduced by 44% (p < 0.001) with no further removal after the second purification step. In patients with a high lymphocyte count (>20 G/L), an improved efficiency of approximately 20% was observed using higher nanoparticle concentrations. A 40 to 50% reduction of B lymphocyte count using alemtuzumab-coupled carbon-coated cobalt nanoparticles is feasible, also in patients with a high lymphocyte count. A second purification step did not further increase removal. This proof-of-concept study demonstrates that such particles allow for the targeted extraction of larger amounts of cellular blood components and might offer new treatment options in the far future. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Magnetic nanosensors have become attractive instruments for the diagnosis and treatment of different diseases. They represent an efficient carrier system in drug delivery or in transporting contrast agents. For such purposes, magnetic nanosensors are used in vivo (intracorporeal application). To remove specific compounds from blood, magnetic nanosensors act as elimination system, which represents an extracorporeal approach. This review discusses principles, advantages and risks on recent advances in the field of magnetic nanosensors. First, synthesis methods for magnetic nanosensors and possibilities for enhancement of biocompatibility with different coating materials are addressed. Then, attention is devoted to clinical applications, in which nanosensors are or may be used as carrier- and elimination systems in the near future. Finally, risk considerations and possible effects of nanomaterials are discussed when working towards clinical applications with magnetic nanosensors. [ABSTRACT FROM AUTHOR]

Recent studies report promising results regarding extracorporeal magnetic separation-based blood purification for the rapid and selective removal of disease-causing compounds from whole blood. High molecular weight compounds, bacteria and cells can be eliminated from blood within minutes, hence offering novel treatment strategies for the management of intoxications and blood stream infections. However, risks associated with incomplete particle separation and the biological consequences of particles entering circulation remain largely unclear. This article discusses the promising future of magnetic separation-based purification while keeping important safety considerations in mind. [ABSTRACT FROM AUTHOR]

Recent studies report promising results regarding extracorporeal magnetic separation-based blood purification for the rapid and selective removal of disease-causing compounds from whole blood. High molecular weight compounds, bacteria and cells can be eliminated from blood within minutes, hence offering novel treatment strategies for the management of intoxications and blood stream infections. However, risks associated with incomplete particle separation and the biological consequences of particles entering circulation remain largely unclear. This article discusses the promising future of magnetic separation-based purification while keeping important safety considerations in mind. [ABSTRACT FROM AUTHOR]

Magnetic nanomaterials find increasing application as separation agents to rapidly isolate target compounds from complex biological media (i.e., blood purification). The responsiveness of the used materials to external magnetic fields (i.e., their saturation magnetization) is one of the most critical parameters for a fast and thorough separation. In the present study, magnetite (Fe3O4) and non-oxidic cementite (Fe3C) based carbon-coated nanomagnets are characterized in detail and compared regarding their separation behavior from human whole blood. A quantification approach for iron-based nanomaterials in biological samples with strong matrix effects (here, salts in blood) based on platinum spiking is shown. Both materials are functionalized with polyethyleneglycol (PEG) to improve cytocompatibility (confirmed by cell toxicity tests) and dispersability. The separation performance is tested in two setups, namely under stationary and different flow-conditions using fresh human blood. The results reveal a superior separation behavior of the cementite based nanomagnets and strongly suggest the use of nanomaterials with high saturation magnetizations for magnetic retention under common blood flow conditions such as in veins. [ABSTRACT FROM AUTHOR]

High magnetic responsiveness is critical for nanomagnets in biomedicine, and fast and complete separation is essential for blood purification or targeted drug delivery, to diminish potential risks. However, studies on the collection efficiency of iron‐based nanoparticles are rare. On page 4888, W. J. Stark and co‐workers present a new quantification approach based on platinum doping of magnetite and carbon‐coated cementite nanoparticles. Their findings show that a good separation efficiency from human whole blood calls for nanomaterials with high saturation magnetizations. [ABSTRACT FROM AUTHOR]