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Title: Liposomal Encapsulation Enhances In Vivo Near Infrared Imaging of Exposed Phosphatidylserine in a Mouse Glioma Model

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 formore » sensitive tumor detection and the potential of utilizing liposomal platform for glioma theranostics.« less

Authors:
 [1];  [1]
  1. Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Radiology
Publication Date:
Research Org.:
Univ. of Texas, Arlington, TX (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
OSTI Identifier:
1628474
Grant/Contract Number:  
FG02-05CH11280
Resource Type:
Accepted Manuscript
Journal Name:
Molecules
Additional Journal Information:
Journal Volume: 18; Journal Issue: 12; Journal ID: ISSN 1420-3049
Publisher:
MDPI
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Biochemistry & Molecular Biology; Chemistry; phosphatidylserine (PS); liposomal nanoprobe; near-infrared (NIR) optical imaging; tumor vasculature; glioma

Citation Formats

Zhang, Liang, and Zhao, Dawen. Liposomal Encapsulation Enhances In Vivo Near Infrared Imaging of Exposed Phosphatidylserine in a Mouse Glioma Model. United States: N. p., 2013. Web. doi:10.3390/molecules181214613.
Zhang, Liang, & Zhao, Dawen. Liposomal Encapsulation Enhances In Vivo Near Infrared Imaging of Exposed Phosphatidylserine in a Mouse Glioma Model. United States. https://doi.org/10.3390/molecules181214613
Zhang, Liang, and Zhao, Dawen. Tue . "Liposomal Encapsulation Enhances In Vivo Near Infrared Imaging of Exposed Phosphatidylserine in a Mouse Glioma Model". United States. https://doi.org/10.3390/molecules181214613. https://www.osti.gov/servlets/purl/1628474.
@article{osti_1628474,
title = {Liposomal Encapsulation Enhances In Vivo Near Infrared Imaging of Exposed Phosphatidylserine in a Mouse Glioma Model},
author = {Zhang, Liang and Zhao, Dawen},
abstractNote = {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.},
doi = {10.3390/molecules181214613},
journal = {Molecules},
number = 12,
volume = 18,
place = {United States},
year = {Tue Nov 26 00:00:00 EST 2013},
month = {Tue Nov 26 00:00:00 EST 2013}
}

Works referenced in this record:

Multimodality Molecular Imaging of Tumor Angiogenesis
journal, June 2008


Recent advances with liposomes as pharmaceutical carriers
journal, February 2005

  • Torchilin, Vladimir P.
  • Nature Reviews Drug Discovery, Vol. 4, Issue 2
  • DOI: 10.1038/nrd1632

Detection of tumor angiogenesis in vivo by αvβ3-targeted magnetic resonance imaging
journal, May 1998

  • Sipkins, Dorothy A.; Cheresh, David A.; Kazemi, Mahmood R.
  • Nature Medicine, Vol. 4, Issue 5
  • DOI: 10.1038/nm0598-623

Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth
journal, September 2009

  • Soman, Neelesh R.; Baldwin, Steven L.; Hu, Grace
  • Journal of Clinical Investigation, Vol. 119, Issue 9
  • DOI: 10.1172/jci38842

Recent advances with liposomes as pharmaceutical carriers
journal, February 2005

  • Torchilin, Vladimir P.
  • Nature Reviews Drug Discovery, Vol. 4, Issue 2
  • DOI: 10.1038/nrd1632

In Vivo Detection of Apoptosis
journal, June 2008


Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes
journal, July 1990


Near-infrared Optical Imaging of Exposed Phosphatidylserine in a Mouse Glioma Model
journal, December 2011

  • Zhao, Dawen; Stafford, Jason H.; Zhou, Heling
  • Translational Oncology, Vol. 4, Issue 6
  • DOI: 10.1593/tlo.11178

Annexin V Staining Due to Loss of Membrane Asymmetry Can Be Reversible and Precede Commitment to Apoptotic Death
journal, August 1999

  • Hammill, Adrienne K.; Uhr, Jonathan W.; Scheuermann, Richard H.
  • Experimental Cell Research, Vol. 251, Issue 1
  • DOI: 10.1006/excr.1999.4581

Understanding and overcoming major barriers in cancer nanomedicine
journal, June 2010


In vivo Off-Resonance Saturation Magnetic Resonance Imaging of α v β 3 -Targeted Superparamagnetic Nanoparticles
journal, February 2009


Tumor targeting using anti-her2 immunoliposomes
journal, July 2001


Annexin V Staining Due to Loss of Membrane Asymmetry Can Be Reversible and Precede Commitment to Apoptotic Death
journal, August 1999

  • Hammill, Adrienne K.; Uhr, Jonathan W.; Scheuermann, Richard H.
  • Experimental Cell Research, Vol. 251, Issue 1
  • DOI: 10.1006/excr.1999.4581

Understanding and overcoming major barriers in cancer nanomedicine
journal, June 2010


Increased Exposure of Phosphatidylethanolamine on the Surface of Tumor Vascular Endothelium
journal, April 2011

  • Stafford, Jason H.; Thorpe, Philip E.
  • Neoplasia, Vol. 13, Issue 4
  • DOI: 10.1593/neo.101366

Endothelial Cell Injury in Cardiovascular Surgery: Ischemia-Reperfusion
journal, December 1996


Imaging of Apoptosis
journal, September 2008


Aminophospholipid Asymmetry: A Matter of Life and Death
journal, March 2003


Phosphatidylserine is a marker of tumor vasculature and a potential target for cancer imaging and therapy
journal, December 2002

  • Ran, Sophia; Thorpe, Philip E.
  • International Journal of Radiation Oncology*Biology*Physics, Vol. 54, Issue 5
  • DOI: 10.1016/s0360-3016(02)03928-7

Binding of vascular anticoagulant alpha (VAC alpha) to planar phospholipid bilayers.
journal, March 1990


Structural and functional characterization of endonexin II, a calcium- and phospholipid-binding protein.
journal, September 1987

  • Schlaepfer, D. D.; Mehlman, T.; Burgess, W. H.
  • Proceedings of the National Academy of Sciences, Vol. 84, Issue 17
  • DOI: 10.1073/pnas.84.17.6078

Advanced strategies in liposomal cancer therapy: Problems and prospects of active and tumor specific drug release
journal, January 2005


Structural and functional characterization of endonexin II, a calcium- and phospholipid-binding protein.
journal, September 1987

  • Schlaepfer, D. D.; Mehlman, T.; Burgess, W. H.
  • Proceedings of the National Academy of Sciences, Vol. 84, Issue 17
  • DOI: 10.1073/pnas.84.17.6078

Dynamic Near-Infrared Optical Imaging of 2-Deoxyglucose Uptake by Intracranial Glioma of Athymic Mice
journal, November 2009


Mobilization of Lysosomal Calcium Regulates the Externalization of Phosphatidylserine during Apoptosis
journal, March 2009

  • Mirnikjoo, Banafsheh; Balasubramanian, Krishnakumar; Schroit, Alan J.
  • Journal of Biological Chemistry, Vol. 284, Issue 11
  • DOI: 10.1074/jbc.m805288200

Dynamic Near-Infrared Optical Imaging of 2-Deoxyglucose Uptake by Intracranial Glioma of Athymic Mice
journal, November 2009


In Vivo Detection of Apoptosis
journal, June 2008


Imaging of Apoptosis
journal, September 2008


Increased Exposure of Phosphatidylethanolamine on the Surface of Tumor Vascular Endothelium
journal, April 2011

  • Stafford, Jason H.; Thorpe, Philip E.
  • Neoplasia, Vol. 13, Issue 4
  • DOI: 10.1593/neo.101366

Nanocarriers as an emerging platform for cancer therapy
journal, December 2007

  • Peer, Dan; Karp, Jeffrey M.; Hong, Seungpyo
  • Nature Nanotechnology, Vol. 2, Issue 12
  • DOI: 10.1038/nnano.2007.387

Pegylated Liposomal Doxorubicin: Metamorphosis of an Old Drug into a New Form of Chemotherapy
journal, January 2001


Radiation-Enhanced Vascular Targeting of Human Lung Cancers in Mice with a Monoclonal Antibody That Binds Anionic Phospholipids
journal, September 2007


Plasma Protein β-2-Glycoprotein 1 Mediates Interaction between the Anti-tumor Monoclonal Antibody 3G4 and Anionic Phospholipids on Endothelial Cells
journal, October 2006

  • Luster, Troy A.; He, Jin; Huang, Xianming
  • Journal of Biological Chemistry, Vol. 281, Issue 40
  • DOI: 10.1074/jbc.m605252200

Works referencing / citing this record:

Convertible MRI contrast: Sensing the delivery and release of anti-glioma nano-drugs
journal, May 2015

  • Zhang, Liang; Zhang, Zhongwei; Mason, Ralph P.
  • Scientific Reports, Vol. 5, Issue 1
  • DOI: 10.1038/srep09874

Phosphatidylserine-Targeted Nanotheranostics for Brain Tumor Imaging and Therapeutic Potential
journal, January 2017


Convertible MRI contrast: Sensing the delivery and release of anti-glioma nano-drugs
journal, May 2015

  • Zhang, Liang; Zhang, Zhongwei; Mason, Ralph P.
  • Scientific Reports, Vol. 5, Issue 1
  • DOI: 10.1038/srep09874

Phosphatidylserine-targeted liposome for enhanced glioma-selective imaging
journal, May 2016