Effects of PVA-coated nanoparticles on human T helper cell activity.

Superparamagnetic iron oxide nanoparticles (SPION) are used as high-sensitive enhancer for magnetic resonance imaging, where they represent a promising tool for early diagnosis of destructive diseases such as rheumatoid arthritis (RA). Since we could demonstrate that professional phagocytes are activated by amino-polyvinyl-alcohol-coated-SPION (a-PVA-SPION), the study here focuses on the influence of a-PVA-SPION on human T cells activity. Therefore, primary human CD4+ T cells from RA patients and healthy subjects were treated with varying doses of a-PVA-SPION for 20h or 72h. T cells were then analyzed for apoptosis, cellular energy, expression of the activation marker CD25 and cell proliferation. Although, we observed that T cells from RA patients are more susceptible to low-dose a-PVA-SPION-induced apoptosis than T cells from healthy subjects, in both groups a-PVA-SPION do not activate CD4+ T cells per se and do not influence mitogen-mediated T cells activation with regard to CD25 expression and cell proliferation. Nevertheless, our results demonstrate that CD4+ T cells from RA patients and healthy subjects differ in their response to mitogen stimulation and oxygen availability. We conclude from our data, that a-PVA-SPION do neither activate nor significantly influence mitogen-stimulated CD4+ T cells activation and have negligible influence on T cells apoptosis.

Significance of surface charge and shell material of superparamagnetic iron oxide nanoparticle (SPION) based core/shell nanoparticles on the composition of the protein corona.

As nanoparticles (NPs) are increasingly used in many applications their safety and efficient applications in nanomedicine have become concerns. Protein coronas on nanomaterials' surfaces can influence how the cell "recognizes" nanoparticles, as well as the in vitro and in vivo NPs' behaviors. The SuperParamagnetic Iron Oxide Nanoparticle (SPION) is one of the most prominent agents because of its superparamagnetic properties, which is useful for separation applications. To mimic surface properties of different types of NPs, a core-shell SPION library was prepared by coating with different surfaces: polyvinyl alcohol polymer (PVA) (positive, neutral and negative), SiO2 (positive and negative), titanium dioxide and metal gold. The SPIONs with different surfaces were incubated at a fixed serum : nanoparticle surface ratio, magnetically trapped and washed. The tightly bound proteins were quantified and identified. The surface charge has a great impact on protein adsorption, especially on PVA and silica where proteins preferred binding to the neutral and positively charged surfaces. The importance of surface material on protein adsorption was also revealed by preferential binding on TiO2 and gold coated SPION, even negatively charged. There is no correlation between the protein net charge and the nanoparticle surface charge on protein binding, nor direct correlation between the serum proteins' concentration and the proteins detected in the coronas.

Effects of PVA coated nanoparticles on human immune cells.

Nanotechnology provides new opportunities in human medicine, mainly for diagnostic and therapeutic purposes. The autoimmune disease rheumatoid arthritis (RA) is often diagnosed after irreversible joint structural damage has occurred. There is an urgent need for a very early diagnosis of RA, which can be achieved by more sensitive imaging methods. Superparamagnetic iron oxide nanoparticles (SPION) are already used in medicine and therefore represent a promising tool for early diagnosis of RA. The focus of our work was to investigate any potentially negative effects resulting from the interactions of newly developed amino-functionalized amino-polyvinyl alcohol coated (a-PVA) SPION (a-PVA-SPION), that are used for imaging, with human immune cells. We analyzed the influence of a-PVA-SPION with regard to cell survival and cell activation in human whole blood in general, and in human monocytes and macrophages representative of professional phagocytes, using flow cytometry, multiplex suspension array, and transmission electron microscopy. We found no effect of a-PVA-SPION on the viability of human immune cells, but cytokine secretion was affected. We further demonstrated that the percentage of viable macrophages increased on exposure to a-PVA-SPION. This effect was even stronger when a-PVA-SPION were added very early in the differentiation process. Additionally, transmission electron microscopy analysis revealed that both monocytes and macrophages are able to endocytose a-PVA-SPION. Our findings demonstrate an interaction between human immune cells and a-PVA-SPION which needs to be taken into account when considering the use of a-PVA-SPION in human medicine.

Nanoparticles in medicine: Current challenges facing inorganic nanoparticle toxicity assessments and standardizations.

Although nanoparticles research is ongoing since more than 30years, the development of methods and standard protocols required for their safety and efficacy testing for human use is still in development. The review covers questions on toxicity, safety, risk and legal issues over the lifecycle of inorganic nanoparticles for medical applications. The following topics were covered: (i) In vitro tests may give only a very first indication of possible toxicity as in the actual methods interactions at systemic level are mainly neglected; (ii) the science-driven and the regulation-driven approaches do not really fit for decisive strategies whether or not a nanoparticle should be further developed and may receive a kind of "safety label". (iii) Cost and time of development are the limiting factors for the drug pipeline. Knowing which property of a nanoparticle makes it toxic it may be feasible to re-engineer the particle for higher safety (safety by design). FROM THE CLINICAL EDITOR: Testing the safety and efficacy of nanoparticles for human use is still in need of standardization. In this concise review, the author described and discussed the current unresolved issues over the application of inorganic nanoparticles for medical applications.

Nanotechnology in medicine: European research and its implications.

In this study, we explore and discuss nanoparticles and nanoscale materials and their use in medicine (nanomedicine) and pharmaceutics (nanopharmaceutics). The study is aimed at shedding light on this highly multidisciplinary research field and at examining the influence of research funding, industrial applications, and legal and regulatory frameworks on the research in this field, a clear understanding of which is essential to efficiently support the translation of research findings into industrial and clinical applications and to enable access to a larger society.

Longitudinal change in femorotibial cartilage thickness and subchondral bone plate area in male and female adolescent vs. mature athletes.

Little is known about changes in human cartilage thickness and subchondral bone plate area (tAB) during growth. The objective of this study was to explore longitudinal change in femorotibial cartilage thickness and tAB in adolescent athletes, and to compare these data with those of mature former athletes. Twenty young (baseline age 16.0 ± 0.6 years) and 20 mature (46.3 ± 4.7 years) volleyball athletes were studied (10 men and 10 women in each group). Magnetic resonance images were acquired at baseline and at year 2-follow-up, and longitudinal changes in cartilage thickness and tAB were determined quantitatively after segmentation. The yearly increase in total femorotibial cartilage thickness was 0.8% (95% confidence interval [CI]: -0.5; 2.1%) in young men and 1.4% (95% CI: 0.7; 2.2%) in young women; the gain in tAB was 0.4% (95% CI: -0.1; 0.8%) and 0.7% (95% CI: 0.2; 1.2%), respectively (no significant difference between sexes). The cartilage thickness increase was greatest in the medial femur, and was not significantly associated with the variability in tAB growth (r=-0.19). Mature athletes showed smaller gains in tAB, and lost >1% of femorotibial cartilage per annum, with the greatest loss observed in the lateral tibia. In conclusion, we find an increase in cartilage thickness (and some in tAB) in young athletes toward the end of adolescence. This increase appeared somewhat greater in women than men, but the differences between both sexes did not reach statistical significance. Mature (former) athletes displayed high rates of (lateral) femorotibial cartilage loss, potentially due to a high prevalence of knee injuries.

Superparamagnetic nanoparticles - a tool for early diagnostics.

Nanoparticles show several interesting new physical and biological properties and therefore play an increasing role in pharmaceutics and medicine. For more than 30 years this research field has been developing slowly but steadily from physical and biological interest (bench) to applications in clinics (bedside). However, many of these particles for biomedical applications are still in the pre-clinical or clinical phase. Combined with drugs or genes these nanoparticles may change the viability of or the transcription processes in cells, which make them interesting for the pharmaceutical industry, cell biology and diagnostics. Because most of the application of superparamagnetic nanoparticles as therapeutic tool, like non-viral vector, drug delivery, are still far from clinical use, this review will concentrate on superparamagnetic nanoparticles as versatile agent for early diagnosis, including the use of such particles as contrast agent for MR imaging and as vehicle for the detection of biomarkers.

Enhancement of the efficiency of non-viral gene delivery by application of pulsed magnetic field.

New approaches to increase the efficiency of non-viral gene delivery are still required. Here we report a simple approach that enhances gene delivery using permanent and pulsating magnetic fields. DNA plasmids and novel DNA fragments (PCR products) containing sequence encoding for green fluorescent protein were coupled to polyethylenimine coated superparamagnetic nanoparticles (SPIONs). The complexes were added to cells that were subsequently exposed to permanent and pulsating magnetic fields. Presence of these magnetic fields significantly increased the transfection efficiency 40 times more than in cells not exposed to the magnetic field. The transfection efficiency was highest when the nanoparticles were sedimented on the permanent magnet before the application of the pulsating field, both for small (50 nm) and large (200-250 nm) nanoparticles. The highly efficient gene transfer already within 5 min shows that this technique is a powerful tool for future in vivo studies, where rapid gene delivery is required before systemic clearance or filtration of the gene vectors occurs.