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Folate receptor targeting of radiolabeled liposomes reduces intratumoral liposome accumulation in human KB carcinoma xenografts

Authors Christensen E, Henriksen JR, Jørgensen JT, Amitay Y, Shmeeda H, Gabizon A, Kjær A, Andresen TL, Hansen AE

Received 3 August 2018

Accepted for publication 20 September 2018

Published 19 November 2018 Volume 2018:13 Pages 7647—7656


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Thomas Webster

Esben Christensen,1–3 Jonas R Henriksen,2,4 Jesper T Jørgensen,3 Yasmine Amitay,5 Hilary Shmeeda,5 Alberto A Gabizon,5 Andreas Kjær,3 Thomas L Andresen,1,2 Anders E Hansen1–3

1Department of Micro- and Nanotechnology, DTU Nanotech, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark; 2Center for Nanomedicine and Theranostics, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark; 3Cluster for Molecular Imaging, Department of Biomedical Sciences and Department of Clinical Physiology, Nuclear Medicine & PET, University of Copenhagen and Rigshospitalet, DK-2200 & DK-2100, Copenhagen, Denmark; 4Department of Chemistry, DTU Chemistry, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark; 5Shaare Zedek Medical Center and Hebrew University – School of Medicine, Jerusalem, Israel

Active, ligand-mediated, targeting of functionalized liposomes to folate receptors (FRs) overexpressed on cancer cells could potentially improve drug delivery and specificity. Studies on folate-targeting liposomes (FTLs) have, however, yielded varying results and generally fail to display a clear benefit of FR targeting.
Method: Tumor accumulating potential of FTLs and NTLs were investigated in a FR overexpressing xenograft model by positron emission tomography/computed tomography imaging.
Results: Tumors displayed significantly lower activity of FTLs than NTLs. Furthermore, FTLs displayed worse circulating properties and increased liver-accumulation than NTLs.
Conclusion: This study underlines that long-circulating properties of liposomes must be achieved to take advantage of EPR-dependent tumor accumulation which may be lost by functionalization. FR-functionalization negatively affected both tumor accumulation and circulation properties.

Keywords: liposomes, folate, cancer, imaging, PET, EPR

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