Research Article

Cell-mediated transfer of catalase nanoparticles from macrophages to brain endothelial, glial and neuronal cells

Center for Drug Delivery & Nanomedicine, University of Nebraska, Omaha, NE, USA

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA

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Yuling Zhao

Center for Drug Delivery & Nanomedicine, University of Nebraska, Omaha, NE, USA

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA

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Shu Li

Center for Drug Delivery & Nanomedicine, University of Nebraska, Omaha, NE, USA

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA

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Sheila M Higginbotham

Center for Drug Delivery & Nanomedicine, University of Nebraska, Omaha, NE, USA

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA

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Stephanie L Booth

Center for Drug Delivery & Nanomedicine, University of Nebraska, Omaha, NE, USA

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA

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Huai-Yun Han

Center for Drug Delivery & Nanomedicine, University of Nebraska, Omaha, NE, USA

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA

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Joseph A Vetro

Center for Drug Delivery & Nanomedicine, University of Nebraska, Omaha, NE, USA

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA

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R Lee Mosley

Center for Drug Delivery & Nanomedicine, University of Nebraska, Omaha, NE, USA

Center for Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE, USA

Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

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Alexander V Kabanov

Center for Drug Delivery & Nanomedicine, University of Nebraska, Omaha, NE, USA

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA

Department of Chemical Enzymology, Faculty of Chemistry, MV Lomonosov Moscow State University, Moscow, Russia

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Howard E Gendelman

Center for Drug Delivery & Nanomedicine, University of Nebraska, Omaha, NE, USA

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA

Center for Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE, USA

Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

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Elena V Batrakova

† Author for correspondence

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Email the corresponding author at ebatrako@unmc.edu

Published Online:20 Sep 2011https://doi.org/10.2217/nnm.11.32

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Abstract

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.

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Published online 20 September 2011

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Acknowledgements

We are grateful to Janice A Taylor and James R Talaska (Confocal Laser Scanning Microscope Core Facility, UNMC) for providing assistance with confocal microscopy and the Nebraska Research Initiative and the Eppley Cancer Center for their support of the Core Facility.

Financial & competing interests disclosure

This study was supported by the NIH grants 1RO1 NS057748 (EVB), 2R01 NS034239 (HEG), 2R37 NS36126 (HEG), P01 NS31492 (HEG), P20RR 15635 (HEG), P01 MH64570 (HEG), P01 NS43985 (HEG), RR021937 (AVK), R021 937-01A2 (JAV), 5R21 EB005683–02 (JAV), BC053471 (JAV), Nebraska Health and Human Services Seed Fund 2007-41 (JAV), and UNMC Eppley Cancer Center Cattlemen’s Seed Fund (JAV). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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