Towards bio-compatible magnetic nanoparticles: Immune-related effects, in-vitro internalization, and in-vivo bio-distribution of zwitterionic ferrite nanoparticles with unexpected renal clearance.

HYPOTHESIS: Iron oxide and other ferrite nanoparticles have not yet found widespread application in the medical field since the translation process faces several big hurdles. The incomplete knowledge of the interactions between nanoparticles and living organisms is an unfavorable factor. This complex subject should be made simpler by synthesizing magnetic nanoparticles with good physical (relaxivity) and chemical (colloidal stability, anti-fouling) properties and no biological activity (no immune-related effects, minimal internalization, fast clearance). Such an innocent scaffold is the main aim of the present paper. We systematically searched for it within the class of small-to-medium size ferrite nanoparticles coated by small (zwitter)ionic ligands. Once established, it can be functionalized to achieve targeting, drug delivery, etc. and the observed biological effects will be traced back to the functional molecules only, as the nanosized scaffold is innocent. EXPERIMENTS: We synthesized nine types of magnetic nanoparticles by systematic variation of core composition, size, coating. We investigated their physico-chemical properties and interaction with serum proteins, phagocytic microglial cells, and a human model of inflammation and studied their biodistribution and clearance in healthy mice. The nanoparticles have good magnetic properties and their surface charge is determined by the preferential adsorption of anions. All nanoparticle types can be considered as immunologically safe, an indispensable pre-requisite for medical applications in humans. All but one type display low internalization by microglial BV2 cells, a process strongly affected by the nanoparticle size. Both small (3 nm) and medium size (11 nm) zwitterionic nanoparticles are in part captured by the mononuclear phagocyte system (liver and spleen) and in part rapidly (≈1 h) excreted through the urinary system of mice. FINDINGS: The latter result questions the universality of the accepted size threshold for the renal clearance of nanoparticles (5.5 nm). We suggest that it depends on the nature of the circulating particles. Renal filterability of medium-size magnetic nanoparticles is appealing because they share with small nanoparticles the decreased accumulation-related toxicity while performing better as magnetic diagnostic/therapeutic agents thanks to their larger magnetic moment. In conclusion, many of our nanoparticle types are a bio-compatible innocent scaffold with unexpectedly favorable clearance.

Zwitterion-Coated Iron Oxide Nanoparticles: Surface Chemistry and Intracellular Uptake by Hepatocarcinoma (HepG2) Cells.

Nanoparticles (NPs) have received much attention in recent years for their diverse potential biomedical applications. However, the synthesis of NPs with desired biodistribution and pharmacokinetics is still a major challenge, with NP size and surface chemistry being the main factors determining the behavior of NPs in vivo. Here we report on the surface chemistry and in vitro cellular uptake of magnetic iron oxide NPs coated with zwitterionic dopamine sulfonate (ZDS). ZDS-coated NPs were compared to similar iron oxide NPs coated with PEG-like 2-[2-(2-methoxyethoxy)ethoxy]acetic acid (MEEA) to investigate how surface chemistry affects their in vitro behavior. ZDS-coated NPs had a very dense coating, guaranteeing high colloidal stability in several aqueous media and negligible interaction with proteins. Treatment of HepG2 cells with increasing doses (2.5-100 µg Fe/mL) of ZDS-coated iron oxide NPs had no effect on cell viability and resulted in a low, dose-dependent NP uptake, inferior than most reported data for the internalization of iron oxide NPs by HepG2 cells. MEEA-coated NPs were scarcely stable and formed micrometer-sized aggregates in aqueous media. They decreased cell viability for dose ≥50 µg Fe/mL, and were more efficiently internalized than ZDS-coated NPs. In conclusion, our data indicate that the ZDS layer prevented both aggregation and sedimentation of iron oxide NPs and formed a biocompatible coating that did not display any biocorona effect. The very low cellular uptake of ZDS-coated iron NPs can be useful to achieve highly selective targeting upon specific functionalization.

In situ infrared emission spectroscopy for quantitative gas-phase measurement under high temperature reaction conditions: an analytical method for methane by means of an innovative small-volume flowing cell.

We have used infrared emission spectroscopy (IRES) in order to perform in situ studies under flowing gas-phase conditions. When the small-volume cell developed herein is used, we can (1) observe emission spectra from a hot gas-phase sample having an effective volume much less than one milliliter, (2) observe spectra of typical molecular species present, and (3) observe spectra of the more important molecular species down to below 10% and in some cases even as low as 1%. In addition, an analytical method has been derived in order to conduct quantitative studies under typical reaction conditions. We show that simplifications can be made in the data acquisition and handling for a direct linear correlation between band intensity and concentration with only simple background correction. The practical lower limit for methane in the present setup is approximately 0.5-1% v/v depending on the selected temperature. Our data were collected at 500, 600, and 700 degrees C, respectively. The major features of the present cell design are fairly simple and basically formed by a quartz tube (outer diameter=6 mm, inner diameter=4 mm) inside a metal pipe and two tubular ceramic heaters. This simple setup has advantages and attractive features that have extended the application of IRES to new fields and, in particular, for in situ studies of hydrocarbon reactions at different residence times at high temperature.

(I(2))(n) encapsulation inside TiO(2): a way to tune photoactivity in the visible region.

We report on the synthesis of nanovoid-structured TiO(2) material via a sol-gel route using titanium isopropoxide as precursor. The nanovoids are formed during the thermal treatment in air at 773 K. The surfaces of internal cavities are populated by the partial oxidation products of the organic part of the Ti precursor (CO(2), hydrogen carbonates, and residual isopropoxide groups). The thermal treatment in air at 773 K allows the maintainence, in the internal voids, of the encapsulated species. Addition of iodine in the synthesis procedure results in a new nanovoid-structured titanium oxide able to absorb light in the whole visible part of the electromagnetic spectrum. The origin of this absorption is attributed to the presence of (I(2))(n) adducts encapsulated in the nanocavities. These species coexist with partial combustion products of isopropoxide groups. Due to the protection of the TiO(2) walls, the (I(2))(n) adducts are not destroyed by thermal treatments in air. We have investigated whether the electron promoted in the excited state of the dye molecule (upon absorption of visible light from the (I(2))(n) adducts) can be injected into either the TiO(2) conduction band or some titanium-localized acceptor, followed by migration of the injected electron to the surface where it reduces adsorbed organic molecules. Preliminarily experiments conducted with sunlight show that the surface-specific efficiency of this process, tested by following the degradation of methylene blue, is about 10 times higher than that of the P25 commercial TiO(2) photocatalyst.