Journal
NANOMEDICINE
Volume 6, Issue 7, Pages 1215-1230Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/NNM.11.32
Keywords
blood-brain barrier; bone marrow-derived macrophages; cell-mediated drug delivery; intercellular communication; Parkinson's disease
Funding
- NIH [1RO1 NS057748, 2R01 NS034239, 2R37 NS36126, P01 NS31492, P20RR 15635, P01 MH64570, P01 NS43985, RR021937, R021 937-01A2, 5R21 EB005683-02, BC053471]
- Nebraska Health and Human Services [2007-41]
- UNMC Eppley Cancer Center
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Background: Our laboratories forged the concept of macrophage delivery of protein antioxidants to attenuate neuroinflammation and nigrostriatal neurodegeneration in Parkinson's disease. Notably, the delivery of the redox enzyme, catalase, incorporated into a polyion complex micelle ('nanozyme') by bone marrow-derived macrophages protected nigrostriatum against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication. Nonetheless, how macrophage delivery of nanozyme increases the efficacy of catalase remains unknown. Methods: In this study, we examined the transfer of nanozyme from macrophages to brain microvessel endothelial cells, neurons and astrocytes. Results: Facilitated transport of the nanozyme from macrophages to endothelial, neuronal and glial target cells occurred through endocytosis-independent mechanisms that involved fusion of cellular membranes, macrophage bridging conduits and nanozyme lipid coatings. Nanozyme transfer was operative across an artificial blood-brain barrier and showed efficient reactive oxygen species decomposition. Conclusion: This is the first demonstration, to our knowledge, that drug-loaded macrophages discharge particles to contiguous target cells for therapeutic brain enzyme delivery. The data shown are of potential value for the treatment of neurodegenerative disorders and notably, Parkinson's disease.
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