Liposome-encapsulated superoxide dismutase mimetic: theranostic potential of an MR detectable and neuroprotective agent
UMass Chan Affiliations
Department of RadiologyDocument Type
Journal ArticlePublication Date
2014-05-01
Metadata
Show full item recordAbstract
Endogenous manganese based superoxide dismutase (Mn-SOD) provides the primary defense against excess production of potentially toxic superoxide anion (O2 (-) ). M40401 is a synthetic enzyme mimetic that has a catalytic activity rate exceeding that of the native SOD enzymes. The presence of a paramagnetic Mn(II) cation in M40401 suggests that the delivery and spatial distribution of this enzyme mimetic in vivo may be directly detectible using magnetic resonance imaging (MRI); however, the cardiotoxicity of Mn(II) severely limits the use of free M40401 in living systems. To deliver M40401 in vivo in amounts sufficient for MRI detection and to limit potential cardiotoxicity, we encapsulated M40401 into 170 nm liposomes composed of phosphatidylcholine and PEGylated phosphatidylethanolamine to achieve extended circulation in the bloodstream. The obtained liposomes efficiently catalyzed superoxide dismutation in vitro. Using 3 T MRI we investigated the biokinetics of liposome-encapsulated M40401 in mice and found that, in addition to catalyzing superoxide dismutation in vitro, M40401 caused differential and region-specific enhancement of mouse brain after systemic administration. Thus, liposome encapsulated M40401 is an ideal candidate for development as a theranostic compound useful for simultaneous MRI-mediated tracking of delivery as well as for neuroprotective treatment of ischemic brain.Source
Contrast Media Mol Imaging. 2014 May-Jun;9(3):221-8. doi: 10.1002/cmmi.1559. Link to article on publisher's siteDOI
10.1002/cmmi.1559Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48608PubMed ID
24700749Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1002/cmmi.1559