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Movement of magnetic nanoparticles in brain tissue: mechanisms and impact on normal neuronal function.

ABSTRACT: UNLABELLED:Magnetic nanoparticles (MNPs) have been used as effective vehicles for targeted delivery of theranostic agents in the brain. The advantage of magnetic targeting lies in the ability to control the concentration and distribution of therapy to a desired target region using external driving magnets. In this study, we investigated the behavior and safety of MNP motion in brain tissue. We found that MNPs move and form nanoparticle chains in the presence of a uniform magnetic field, and that this chaining is influenced by the applied magnetic field intensity and the concentration of MNPs in the tissue. Using electrophysiology recordings, immunohistochemistry and fluorescent imaging we assessed the functional health of neurons and neural circuits and found no adverse effects associated with MNP motion through brain tissue. FROM THE CLINICAL EDITOR:Much research has been done to test the use of nanocarriers for gaining access across the blood brain barrier (BBB). In this respect, magnetic nanoparticles (MNPs) are one of the most studied candidates. Nonetheless, the behavior and safety of MNP once inside brain tissue remains unknown. In this article, the authors thus studied this very important subject.

SUBMITTER: Ramaswamy B

PROVIDER: S-EPMC4586396 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Movement of magnetic nanoparticles in brain tissue: mechanisms and impact on normal neuronal function.

Ramaswamy Bharath B Kulkarni Sandip D SD Villar Pablo S PS Smith Richard S RS Eberly Christian C Araneda Ricardo C RC Depireux Didier A DA Shapiro Benjamin B

Nanomedicine : nanotechnology, biology, and medicine 20150624 7

Magnetic nanoparticles (MNPs) have been used as effective vehicles for targeted delivery of theranostic agents in the brain. The advantage of magnetic targeting lies in the ability to control the concentration and distribution of therapy to a desired target region using external driving magnets. In this study, we investigated the behavior and safety of MNP motion in brain tissue. We found that MNPs move and form nanoparticle chains in the presence of a uniform magnetic field, and that this chain ...[more]

PMID: 26115639

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Project description:White adipose tissue (WAT) is becoming widely used in regenerative medicine/cell therapy applications, and its physiological and pathological importance is increasingly appreciated. WAT is a complex organ composed of differentiated adipocytes, stromal mesenchymal progenitors known as adipose stromal cells (ASC), as well as endothelial vascular cells and infiltrating leukocytes. Two-dimensional (2D) culture that has been typically used for studying adipose cells does not adequately recapitulate WAT complexity. Improved methods for reconstruction of functional WAT ex vivo are instrumental for understanding of physiological interactions between the composing cell populations. Here, we used a three-dimensional (3D) levitation tissue culture system based on magnetic nanoparticle assembly to model WAT development and growth in organoids termed adipospheres. We show that 3T3-L1 preadipocytes remain viable in spheroids for a long period of time, while in 2D culture, they lose adherence and die after reaching confluence. Upon adipogenesis induction in 3T3-L1 adipospheres, cells efficiently formed large lipid droplets typical of white adipocytes in vivo, while only smaller lipid droplet formation is achievable in 2D. Adiposphere-based coculture of 3T3-L1 preadipocytes with murine endothelial bEND.3 cells led to a vascular-like network assembly concomitantly with lipogenesis in perivascular cells. Adipocyte-depleted stromal vascular fraction (SVF) of mouse WAT cultured in 3D underwent assembly into organoids with vascular-like structures containing luminal endothelial and perivascular stromal cell layers. Adipospheres made from primary WAT cells displayed robust proliferation and complex hierarchical organization reflected by a matricellular gradient incorporating ASC, endothelial cells, and leukocytes, while ASC quickly outgrew other cell types in adherent culture. Upon adipogenesis induction, adipospheres derived from the SVF displayed more efficient lipid droplet accumulation than 2D cultures. This indicates that 3D intercellular signaling better recapitulates WAT organogenesis. Combined, our studies show that adipospheres are appropriate for WAT modeling ex vivo and provide a new platform for functional screens to identify molecules bioactive toward individual adipose cell populations. This 3D methodology could be adopted for WAT transplantation applications and aid approaches to WAT-based cell therapy.

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Movement of magnetic nanoparticles in brain tissue: mechanisms and impact on normal neuronal function.

Publications

Movement of magnetic nanoparticles in brain tissue: mechanisms and impact on normal neuronal function.

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