Abstract
We have previously demonstrated that exposed phosphatidylserine (PS) on tumor vascular endothelial cells is highly tumor specific, and development of the PS targeted near infrared (NIR) optical probe enables successful in vivo optical imaging of U87 gliomas in a mouse model. Liposomes have been widely used as a nanovector for delivery of chemotherapeutics and imaging contrast agents due to their high payload and longer circulation time. In the current study, we have fabricated PS-targeted liposomal nanoprobes encapsulating a NIR dye, IRDye® 800CW, aiming to enhance PS-targeted tumor imaging. Hydrophilic 800CW dye was packed into the core of polyethylene glycol (PEG)-coated liposomes functionalized with F(ab’)2 fragments of PGN635, a fully human monoclonal antibody that binds PS. As expected, in vivo dynamic NIR imaging revealed significantly improved tumor/normal contrast (TNR = 20 ± 3; p < 0.01) of subcutaneous U87 gliomas in mice after injection of the liposomal nanoprobes. Markedly enhanced TNR was observed after the tumors were irradiated to increase PS exposure (TNR = 48 ± 6; p < 0.05). Intriguingly, the liposomal nanoprobes, PGN-L-800CW showed distinct biodistribution and pharmacokinetics compared to the 800CW-PGN probes used in our previous study. Our data further suggest the usefulness of PS-targeted imaging probes for sensitive tumor detection and the potential of utilizing liposomal platform for glioma theranostics.
Highlights
Development of tumor-specific imaging probes is critical for improved tumor targeting and enhanced localization of tumors by diagnostic imaging
Much interest has been generated in developing molecular imaging probes that bind to the exposed PS in order to noninvasively monitor the response of cancer treatment
After characterization of the chemical and physical properties of the nanoprobes and confirmation of their in vitro binding specificity, we investigated the in vivo behavior of PGN-L-800CW in subcutaneous U87 glioma bearing mice, the same model as used in our previous study, which enabled a direct comparison between the two probes
Summary
Development of tumor-specific imaging probes is critical for improved tumor targeting and enhanced localization of tumors by diagnostic imaging. The PS exposed endothelial cells are viable and not subject to apoptotic processes [6,7] These cells that are not co-stained by anti-active caspase 3 antibody can resume growth and reestablish phospholipid asymmetry, which enable them to evade immune surveillance [8,9]. He et al further investigated the differential sensitivity between tumor vascular endothelial cells and tumor cells in response to a total of 10 Gy radiation in lung A549 tumors. After systemic injection of 800CW-PGN635, in vivo NIR imaging successfully detected significant uptake of the probes by U87 glioma xenografts in mice [10]. Nanoprobes and confirmation of their in vitro binding specificity, we investigated the in vivo behavior of PGN-L-800CW in subcutaneous U87 glioma bearing mice, the same model as used in our previous study, which enabled a direct comparison between the two probes
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