Kirsten M. Pondman

Complement activation by carbon nanotubes and its influence on the phagocytosis and cytokine response by macrophages

UNLABELLED Carbon nanotubes (CNTs) have promised a range of applications in biomedicine. Although influenced by the dispersants used, CNTs are recognized by the innate immune system, predominantly by the classical pathway of the complement system. Here, we confirm that complement activation by the CNT used continues up to C3 and C5, indicating that the entire complement system is activated including the formation of membrane-attack complexes. Using recombinant forms of the globular regions of human C1q (gC1q) as inhibitors of CNT-mediated classical pathway activation, we show that C1q, the first recognition subcomponent of the classical pathway, binds CNTs via the gC1q domain. Complement opsonisation of CNTs significantly enhances their uptake by U937 cells, with concomitant downregulation of pro-inflammatory cytokines and up-regulation of anti-inflammatory cytokines in both U937 cells and human monocytes. We propose that CNT-mediated complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response. FROM THE CLINICAL EDITOR This study highlights the importance of the complement system in response to carbon nanontube administration, suggesting that the ensuing complement activation may cause recruitment of cellular infiltration, followed by phagocytosis without inducing a pro-inflammatory immune response.

Uptake and transport of superparamagnetic iron oxide nanoparticles through human brain capillary endothelial cells.

The blood-brain barrier (BBB) formed by brain capillary endothelial cells (BCECs) constitutes a firm physical, chemical, and immunological barrier, making the brain accessible to only a few percent of potential drugs intended for treatment inside the central nervous system. With the purpose of overcoming the restraints of the BBB by allowing the transport of drugs, siRNA, or DNA into the brain, a novel approach is to use superparamagnetic iron oxide nanoparticles (SPIONs) as drug carriers. The aim of this study was to investigate the ability of fluorescent SPIONs to pass through human brain microvascular endothelial cells facilitated by an external magnet. The ability of SPIONs to penetrate the barrier was shown to be significantly stronger in the presence of an external magnetic force in an in vitro BBB model. Hence, particles added to the luminal side of the in vitro BBB model were found in astrocytes cocultured at a remote distance on the abluminal side, indicating that particles were transported through the barrier and taken up by astrocytes. Addition of the SPIONs to the culture medium did not negatively affect the viability of the endothelial cells. The magnetic force-mediated dragging of SPIONs through BCECs may denote a novel mechanism for the delivery of drugs to the brain.

Au coated Ni nanowires with tuneable dimensions for biomedical applications

Due to their shape anisotropy, high aspect ratio magnetic nanoparticles offer many advantages in biomedical applications. For biocompatibility, it is essential to have full control over the dimensions and surface chemistry of the particles. The aim of this study was to synthesize biocompatible nanowires with tuneable dimensions. This was achieved by electrodeposition of Ni in polycarbonate membranes. To ensure biocompatibility, a continuous gold coating was deposited onto the Ni wires by a newly developed electroless deposition method. The coating was analysed using electron microscopy and X-ray diffraction. Magnetic properties, anisotropy and Au film thickness were studied using vibrating sample magnetometry. After biofunctionalization, no significant cytotoxic effects were found in studies involving a diverse range of primary and tumour cells exposed to increasing concentrations of nanowires for up to 7 days. These nanowires may thus be used for in vivo applications such as magnetic drug delivery.

Soft Magnets from the Self‐Organization of Magnetic Nanoparticles in Twisted Liquid Crystals

Organizing magnetic nanoparticles into long-range and dynamic assemblies would not only provide new insights into physical phenomena but also open opportunities for a wide spectrum of applications. In particular, a major challenge consists of the development of nanoparticle-based materials for which the remnant magnetization and coercive field can be controlled at room temperature. Our approach consists of promoting the self-organization of magnetic nanoparticles in liquid crystals (LCs). Using liquid crystals as organizing templates allows us to envision the design of tunable self-assemblies of magnetic nanoparticles, because liquid crystals are known to reorganize under a variety of external stimuli. Herein, we show that twisted liquid crystals can be used as efficient anisotropic templates for superparamagnetic nanoparticles and demonstrate the formation of hybrid soft magnets at room temperature.

Recognition of Carbon Nanotubes by the Human Innate Immune System

A major function of the human innate immune system is to recognize non-self: i.e., invading microorganisms or altered, damaged self macromolecules and cells. Various components of the human immune system recognize foreign synthetic materials, including carbon nanotubes (CNTs). The complement system proteins in blood, and the collectins, SP-A and SP-D in the lungs bind to carbon nanotubes, in competition with other plasma proteins, and may influence their subsequent adhesion to and uptake by cells and their localization in the body. Modification of the surface chemistry of carbon nanotubes alters their binding to complement proteins and collectins, and provides information on the mechanism by which binding of these proteins occurs.

Magnetic Nanoparticles for Diagnosis and Medical Therapy

Magnetic nanoparticles (MNPs) reveal promising opportunities for biomedical applications, potentially allowing minimally invasive diagnosis and therapeutic usage at several levels of human body organization (cells, tissue and organs). An increasingly broad collection of MNPs has been recently developed not only at the research level but also in some specific cases for medical applications. Superparamagnetic iron oxide (SPIO) nanoparticles are commonly used in clinical practice as contrast agents for magnetic resonance imaging (MRI) of liver and angiography. Carbon nanotubes (CNTs) are another type of nanomaterials with great potential for biomedical applications. Filled with ferromagnetic materials, an ensemble of aligned CNTs displays a highly non-linear, anisotropic and hysteretic magnetization behaviour due to their extremely high aspect ratio (length/diameter >100). The intrinsic properties of such ferromagnetic nanoparticles can potentially improve diagnosis and therapy of numerous diseases. Combining tailored biocompatible ferromagnetic nanomaterials with dedicated detection technology can provide a new approach leading to the exciting perspective of accurate medical imaging and medical therapy (magnetic hyperthermia, targeted drug delivery, etc.) at the cellular level. Elongated Fe-filled CNTs (Fe-CNTs) are foreseen as potential nanotools leading to minimally invasive, highly sensitive, and cost effective novel investigation routes for complete human body systems.