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Nanomedicine (Lond). 2012 Jun;7(6):815-33. doi: 10.2217/nnm.11.156. Epub 2012 Jan 11.

Blood-borne macrophage-neural cell interactions hitchhike on endosome networks for cell-based nanozyme brain delivery.

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  • 1University of Nebraska Medical Center, Omaha, NE, USA.

Abstract

BACKGROUND:

Macrophage-carried nanoformulated catalase ('nanozyme') attenuates neuroinflammation and protects nigrostriatal neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication. This is facilitated by effective enzyme transfer from blood-borne macrophages to adjacent endothelial cells and neurons leading to the decomposition of reactive oxygen species.

MATERIALS & METHODS:

We examined the intra- and inter-cellular trafficking mechanisms of nanozymes by confocal microscopy. Improved neuronal survival mediated by nanozyme-loaded macrophages was demonstrated by fluorescence-activated cell sorting.

RESULTS:

In macrophages, nanozymes were internalized mainly by clathrin-mediated endocytosis then trafficked to recycling endosomes. The enzyme is subsequently released in exosomes facilitated by bridging conduits. Nanozyme transfer from macrophages to adjacent cells by endocytosis-independent mechanisms diffusing broadly throughout the recipient cells. In contrast, macrophage-free nanozymes were localized in lysosomes following endocytic entry.

CONCLUSION:

Facilitated transfer of nanozyme from cell to cell can improve neuroprotection against oxidative stress commonly seen during neurodegenerative disease processes.

PMID:
22236307
[PubMed - indexed for MEDLINE]
PMCID:
PMC3384770
Free PMC Article

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