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Magnetic particle imaging (MPI) has garnered significant attention in biomedical imaging research due to its excellent signal intensity that is generated directly from superparamagnetic iron oxide nanoparticles (SPIONs). Small nanoparticle tracers with high saturation magnetisation are crucial for MPI as they can prolong circulation, crossing the blood brain barrier and enhance cellular uptake. In this work, we demonstrate small zinc doped iron oxide nanoparticles (Zn-IONPs) are excellent MPI tracers. Our Zn-IONPs exhibited up to 37 % and 64% enhancement in saturation magnetisation (Msat) value and MPI signal intensity respectively compared to Fe3O4 of the same size. As a result, the polymer encapsulated Zn-IONPs achieved up to 2.7-fold enhancement in MPI signal intensity compared to VivoTrax. Furthermore, these polymer encapsulated NPs were also determined to be non-toxic hence making these Zn-IONPs ideal for many biomedical applications in MPI where small size is critical to prolong circulation time and crossing the blood brain barrier.

Purpose: Directing nanoparticles to cancer cells without using antibodies is of great interest. Subtle changes to the surface chemistry of nanoparticles can significantly affect their biological fate, including their propensity to associate with different cell populations. For instance, nanoparticles functionalized with thiol-reactive groups can potentially enhance association with cells that over-express cell-surface thiol groups. The potential of such an approach for enhancing drug delivery for childhood acute lymphoblastic leukemia (ALL) cells has not been investigated. Herein, we investigate the impact of thiol-reactive star polymers on the cellular association and the mechanisms of uptake of the nanoparticles. Methods: We prepared fluorescently labeled star polymers functionalized with an mPEG brush corona and pyridyl disulfide to examine how reactivity to exofacial thiols impacts cellular association with ALL cells. We also studied how variations to the mPEG brush composition could potentially be used as a secondary method for controlling the extent of cell association. Specifically, we examined how the inclusion of shorter diethylene glycol brush moieties into the nanoparticle corona could be used to further influence cell association. Results: Star polymers incorporating both thiol-reactive and diethylene glycol brush moieties exhibited the highest cellular association, followed by those functionalized solely with thiol reactive groups compared to control nanoparticles in T and B pediatric ALL patient-derived xenografts harvested from the spleens and bone marrow of immunodeficient mice. Transfection of cells with an early endosomal marker and imaging with correlative light and electron microscopy confirmed cellular uptake. Endocytosis inhibitors revealed dynamin-dependent clathrin-mediated endocytosis as the main uptake pathway for all the star polymers. Conclusion: Thiol-reactive star polymers having an mPEG brush corona that includes a proportion of diethy

Functionalization of super paramagnetic iron oxide NPs (SPIONs) with different coatings renders them with unique physicochemical properties that allow them to be used in a broad range of applications such as drug targeting and water purification. However, it is required to fill the gap between the promises of any new functionalized SPIONs and the effects of these coatings on the NPs safety. Nanotoxicology is offering diverse strategies to assess the effect of exposure to SPIONs in a case-by-case manner but an integrated nanoimpact scale has not been developed yet. We have implemented the classical integrated biological response (IBR) into an integrated nanoimpact index (INI) as an early warning scale of nano-impact based on a combination of toxicological end points such as cell proliferation, oxidative stress, apoptosis and genotoxicity. Here, the effect of SPIONs functionalized with tri-sodium citrate (TSC), polyethylenimine (PEI), aminopropyl-triethoxysilane (APTES) and Chitosan (chitosan) were assessed on human keratinocytes and endothelial cells. Our results show that endothelial cells were more sensitive to exposure than keratinocytes and the initial cell culture density modulated the toxicity. PEI-SPIONs had the strongest effects in both cell types while TSC-SPIONS were the most biocompatible. This study emphasizes not only the importance of surface coatings but also the cell type and the initial cell density on the selection of toxicity assays. The INI developed here could offer an initial rationale to choose either modifying SPIONs properties to reduce its nanoimpact or performing a complete risk assessment to define the risk boundaries., QC 20150911

Ultra-small nanoparticles (USNPs) at 1-3 nm are a subset of nanoparticles (NPs) that exhibit intermediate physicochemical properties between molecular dispersions and larger NPs. Despite interest in their utilization in applications such as theranostics, limited data about their toxicity exist. Here the effect of TiO2-USNPs on endothelial cells in vitro, and zebrafish embryos in vivo, was studied and compared to larger TiO2-NPs (30 nm) and to single walled carbon nanotubes (SWCNTs). In vitro exposure showed that TiO2-USNPs were neither cytotoxic, nor had oxidative ability, nevertheless were genotoxic. In vivo experiment in early developing zebrafish embryos in water at high concentrations of TiO2-USNPs caused mortality possibly by acidifying the water and caused malformations in the form of pericardial edema when injected. Myo1C involved in glomerular development of zebrafish embryos was upregulated in embryos exposed to TiO2-USNPs. They also exhibited anti-angiogenic effects both in vitro and in vivo plus decreased nitric oxide concentration. The larger TiO2-NPs were genotoxic but not cytotoxic. SWCNTs were cytotoxic in vitro and had the highest oxidative ability. Neither of these NPs had significant effects in vivo. To our knowledge this is the first study evaluating the effects of TiO2-USNPs on vascular toxicity in vitro and in vivo and this strategy could unravel USNPs potential applications.

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Contains fulltext : 58559.pdf (publisher's version ) (Closed access), Drug therapy may become difficult when a significant amount of the small intestine is resected, as happens in patients with a short small bowel. Drug absorption from the gastrointestinal tract is altered in these patients; however, this effect is variable in patients and differs with each drug. Literature regarding clinical outcomes of normal or alternative administration routes in patients with a short small bowel is limited. We explored what is written about the normal absorption of commonly used drugs and what difference the resection of different but substantial parts of the small intestine makes. Changes in the gastrointestinal tract after resection of >50% of the small intestine causes malabsorption of macronutrients and micronutrients, and may alter the drug absorption process. The metabolic activity of the abundantly present intestinal lactobacilli can also affect the enteral drug absorption in patients with short small bowel as this results in the production of lactic acid, gaseous CO(2), ethanol and an increased bile acid deconjugation. Accelerated intestinal luminal transit time causes a reduction in absorption of certain antimicrobial agents, digoxin, hydrochlorothiazide, ciclosporin, cimetidine, mesalazine (5-aminosalicylic acid), oral contraceptives and levothyroxine. Gastric hypersecretion and lack of sufficient contact time with the intestinal mucosa in patients with short small bowel leads to insufficient absorption of drugs such as omeprazole. Successful treatment with warfarin, tricyclic antidepressants, metronidazole, fluconazole, procainamide, sotalol and pindolol are reported in several studies. Many different factors cause this variability in drug absorption in such patients. Monitoring the serum drug concentration in these patients may ease dealing with the management problems.