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

Esben Christensen, Jonas R. Henriksen, Jesper T. Jørgensen, Yasmine Amitay, Hilary Schmeeda, Alberto A. Gabizon, Andreas Kjær, Thomas Lars Andresen, Anders Elias Hansen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Background: 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. 
Original languageEnglish
JournalInternational Journal of Nanomedicine
Volume13
Pages (from-to)7647-7656
ISSN1176-9114
DOIs
Publication statusPublished - 2018

Keywords

  • Liposomes
  • Folate
  • Cancer
  • Imaging
  • PET
  • EPR

Cite this

@article{aa0bee4492134eefa37b8bfbcb3e5a5d,
title = "Folate receptor targeting of radiolabeled liposomes reduces intratumoral liposome accumulation in human KB carcinoma xenografts",
abstract = "Background: 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",
author = "Esben Christensen and Henriksen, {Jonas R.} and J{\o}rgensen, {Jesper T.} and Yasmine Amitay and Hilary Schmeeda and Gabizon, {Alberto A.} and Andreas Kj{\ae}r and Andresen, {Thomas Lars} and Hansen, {Anders Elias}",
year = "2018",
doi = "10.2147/IJN.S182579",
language = "English",
volume = "13",
pages = "7647--7656",
journal = "International Journal of Nanomedicine (Online)",
issn = "1176-9114",
publisher = "Dove Press Ltd",

}

Folate receptor targeting of radiolabeled liposomes reduces intratumoral liposome accumulation in human KB carcinoma xenografts. / Christensen, Esben; Henriksen, Jonas R.; Jørgensen, Jesper T.; Amitay, Yasmine; Schmeeda, Hilary; Gabizon, Alberto A.; Kjær, Andreas ; Andresen, Thomas Lars; Hansen, Anders Elias.

In: International Journal of Nanomedicine, Vol. 13, 2018, p. 7647-7656.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Folate receptor targeting of radiolabeled liposomes reduces intratumoral liposome accumulation in human KB carcinoma xenografts

AU - Christensen, Esben

AU - Henriksen, Jonas R.

AU - Jørgensen, Jesper T.

AU - Amitay, Yasmine

AU - Schmeeda, Hilary

AU - Gabizon, Alberto A.

AU - Kjær, Andreas

AU - Andresen, Thomas Lars

AU - Hansen, Anders Elias

PY - 2018

Y1 - 2018

N2 - Background: 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. 

AB - Background: 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. 

KW - Liposomes

KW - Folate

KW - Cancer

KW - Imaging

KW - PET

KW - EPR

U2 - 10.2147/IJN.S182579

DO - 10.2147/IJN.S182579

M3 - Journal article

VL - 13

SP - 7647

EP - 7656

JO - International Journal of Nanomedicine (Online)

JF - International Journal of Nanomedicine (Online)

SN - 1176-9114

ER -