Phosphatidylserine-targeted liposome for enhanced glioma-selective imaging
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Liang Zhang1, Amyn A. Habib2, Dawen Zhao3,4
1Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
2Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center and the North Texas VA Medical Center, Dallas, TX, USA
3Department of Biomedical Engineering, Wake Forest School of Medicine, Winston Salem, NC, USA
4Department of Cancer Biology, Wake Forest School of Medicine, Winston Salem, NC, USA
Dawen Zhao, email: [email protected]
Keywords: phosphatidylserine (PS), blood brain barrier (BBB), glioblastoma multiform, magnetic resonance imaging (MRI), tumor vasculature
Received: February 24, 2016 Accepted: April 28, 2016 Published: May 25, 2016
Phosphatidylserine (PS), which is normally intracellular, becomes exposed on the outer surface of viable endothelial cells (ECs) of tumor vasculature. Utilizing a PS-targeting antibody, we have recently established a PS-targeted liposomal (PS-L) nanoplatform that has demonstrated to be highly tumor-selective. Because of the vascular lumen-exposed PS that is immediately accessible without a need to penetrate the intact blood brain barrier (BBB), we hypothesize that the systemically administered PS-L binds specifically to tumor vascular ECs, becomes subsequently internalized into the cells and then enables its cargos to be efficiently delivered to glioma parenchyma. To test this, we exploited the dual MRI/optical imaging contrast agents-loaded PS-L and injected it intravenously into mice bearing intracranial U87 glioma. At 24 h, both in vivo optical imaging and MRI depicted enhanced tumor contrast, distinct from the surrounding normal brain. Intriguingly, longitudinal MRI revealed temporal and spatial intratumoral distribution of the PS-L by following MRI contrast changes, which appeared punctate in tumor periphery at an earlier time point (4 h), but became clustering and disseminated throughout the tumor at 24 h post injection. Importantly, glioma-targeting specificity of the PS-L was antigen specific, since a control probe of irrelevant specificity showed minimal accumulation in the glioma. Together, these results indicate that the PS-L nanoplatform enables the enhanced, glioma-targeted delivery of imaging contrast agents by crossing the tumor BBB efficiently, which may also serve as a useful nanoplatform for anti-glioma drugs.
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