8 research outputs found
The lateral septum mediates kinship behavior in the rat
Kinship behavior in rodents has been documented in the laboratory setting but the neural mechanisms that mediate kinship behavior are not known. Here, the authors show that the lateral septum has a key role in organizing mammalian kinship behavior
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)Âethoxy]Âacetic 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
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 ( 481 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