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Hyaluronan-conjugated liposomes encapsulating gemcitabine for breast cancer stem cellsopen access

Authors
Han, Na-KyungShin, Dae HwanKim, Jung SeokWeon, Kwon YeonJang, Chang-YoungKim, Jin-Seok
Issue Date
Apr-2016
Publisher
DOVE MEDICAL PRESS LTD
Keywords
breast cancer stem cells; targeting; CD44 surface marker; EPR effect; drug delivery system
Citation
INTERNATIONAL JOURNAL OF NANOMEDICINE, v.11, pp 1413 - 1425
Pages
13
Journal Title
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume
11
Start Page
1413
End Page
1425
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/9852
DOI
10.2147/IJN.S95850
ISSN
1176-9114
1178-2013
Abstract
Investigation of potential therapeutics for targeting breast cancer stem cells (BCSCs) is important because these cells are regarded as culprit of breast cancer relapse. Accomplishing this kind of strategy requires a specific drug-delivery system using the distinct features of liposomes. Studies on targeted liposomal delivery systems have indicated the conjugation of hyaluronan (HA), a primary ligand for CD44 surface markers, as an appropriate method for targeting BCSCs. For this study, enriched BCSCs were obtained by culturing MCF-7 breast cancer cells in nonadherent conditions. The enriched BCSCs were challenged with HA-conjugated liposomes encapsulating gemcitabine (2, 2-difluoro-2-deoxycytidine, GEM). In vitro study showed that the HA-conjugated liposomes significantly enhanced the cytotoxicity, anti-migration, and anti-colony formation abilities of GEM through targeting of CD44 expressed on BCSCs. In pharmacokinetic study, area under the drug concentration vs time curve (AUC) of the immunoliposomal GEM was 3.5 times higher than that of free GEM, indicating that the HA-conjugated liposomes enhanced the stability of GEM in the bloodstream and therefore prolonged its half-life time. The antitumor effect of the immunoliposomal GEM was 3.3 times higher than that of free GEM in a xenograft mouse model, probably reflecting the unique targeting of the CD44 receptor by HA and the increased cytotoxicity and stability through the liposomal formulation. Furthermore, marginal change in body weight demonstrated that the use of liposomes considerably reduced the systemic toxicity of GEM on normal healthy cells. Taken together, this study demonstrates that HA-conjugated liposomes encapsulating GEM show promise for the therapy of breast cancer in vitro and in a xenograft model by targeting the BCSCs.
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