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Enhanced delivery of liposomes to lung tumor through targeting interleukin-4 receptor on both tumor cells and tumor endothelial cells

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Author(s)
Lianhua ChiMoon-Hee NaHyun-Kyung JungSri Murugan Poongkavithai VadevooCheong-Wun KimGuruprasath PadmanabanTae-In ParkJae-Yong ParkIlseon HwangKeon Uk ParkFrank LiangMaggie LugJiho ParkIn-San KimByung-Heon Lee
Keimyung Author(s)
Park, Keon UkHwang, Il Seon
Department
Dept. of Internal Medicine (내과학)
Dept. of Pathology (병리학)
Journal Title
Journal of Controlled Release
Issued Date
2015
Volume
209
Keyword
IL-4 receptorLiposomesLung tumorTargeted drug delivery
Abstract
A growing body of evidence suggests that pathological lesions express tissue-specific molecular targets or biomarkerswithin
the tissue. Interleukin-4 receptor (IL-4R) is overexpressed inmany types of cancer cells, including
lung cancer. Herewe investigated the properties of IL-4R-binding peptide-1 (IL4RPep-1), a CRKRLDRNC peptide,
and its ability to target the delivery of liposomes to lung tumor. IL4RPep-1 preferentially bound to H226 lung
tumor cells which express higher levers of IL-4R compared to H460 lung tumor cells which express less IL-4R.
Mutational analysis revealed that C1, R2, and R4 residues of IL4RPep-1 were the key binding determinants.
IL4RPep-1-labeled liposomes containing doxorubicin were more efficiently internalized in H226 cells and effectively
delivered doxorubicin into the cells compared to unlabeled liposomes. In vivo fluorescence imaging of nude
mice subcutaneously xenotransplanted with H226 tumor cells indicated that IL4RPep-1-labeled liposomes
accumulatemore efficiently in the tumor and inhibit tumor growth more effectively compared to unlabeled liposomes.
Interestingly, expression of IL-4Rwas high in vascular endothelial cells of tumor, while littlewas detected
in vascular endothelial cells of control organs including the liver. IL-4R expression in cultured human vascular endothelial
cells was also up-regulated when activated by a pro-inflammatory cytokine tumor necrosis factor-α.
Moreover, the up-regulation of IL-4R expression was observed in primary human lung cancer tissues. These
results indicate that IL-4R-targeting nanocarriers may be a useful strategy to enhance drug delivery through
the recognition of IL-4R in both tumor cells and tumor endothelial cells.
Keimyung Author(s)(Kor)
박건욱
황일선
Publisher
School of Medicine
Citation
Lianhua Chi et al. (2015). Enhanced delivery of liposomes to lung tumor through targeting interleukin-4 receptor on both tumor cells and tumor endothelial cells. Journal of Controlled Release, 209, 327–336. doi: 10.1016/j.jconrel.2015.05.260
Type
Article
ISSN
0168-3659
Source
https://www.sciencedirect.com/science/article/pii/S0168365915005581?via%3Dihub
DOI
10.1016/j.jconrel.2015.05.260
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/32963
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
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