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

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 Lu, Jiho Park, In San Kim, Byung Heon Lee

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

A growing body of evidence suggests that pathological lesions express tissue-specific molecular targets or biomarkers within the tissue. Interleukin-4 receptor (IL-4R) is overexpressed in many types of cancer cells, including lung cancer. Here we 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 accumulate more efficiently in the tumor and inhibit tumor growth more effectively compared to unlabeled liposomes. Interestingly, expression of IL-4R was high in vascular endothelial cells of tumor, while little was 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.

Original languageEnglish
Pages (from-to)327-336
Number of pages10
JournalJournal of Controlled Release
Volume209
DOIs
Publication statusPublished - 2015 May 28
Externally publishedYes

Keywords

  • IL-4 receptor
  • Liposomes
  • Lung tumor
  • Targeted drug delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

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