Enhanced delivery of liposomes to lung tumor through targeting interleukin-4 receptor on both tumor cells and tumor endothelial cells
- Author(s)
- Lianhua Chi; Moon-Hee Na; Hyun-Kyung Jung; Sri Murugan Poongkavithai Vadevoo; Cheong-Wun Kim; Guruprasath Padmanaban; Tae-In Park; Jae-Yong Park; Ilseon Hwang; Keon Uk Park; Frank Liang; Maggie Lug; Jiho Park; In-San Kim; Byung-Heon Lee
- Keimyung Author(s)
- Park, Keon Uk; Hwang, 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 receptor; Liposomes; Lung tumor; Targeted 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.
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