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Size-controlled, dual-ligand modified liposomes that target the tumor vasculature show promise for use in drug-resistant cancer therapy
Title: | Size-controlled, dual-ligand modified liposomes that target the tumor vasculature show promise for use in drug-resistant cancer therapy |
Authors: | Takara, Kazuhiro Browse this author | Hatakeyama, Hiroto Browse this author →KAKEN DB | Kibria, Golam Browse this author | Ohga, Noritaka Browse this author →KAKEN DB | Hida, Kyoko Browse this author →KAKEN DB | Harashima, Hideyoshi Browse this author →KAKEN DB |
Keywords: | Anti-angiogenesis | Drug delivery | Tumor endothelial cells | Drug resistant tumor | Dual ligand |
Issue Date: | 20-Aug-2012 |
Publisher: | Elsevier B.V. |
Journal Title: | Journal of Controlled Release |
Volume: | 162 |
Issue: | 1 |
Start Page: | 225 |
End Page: | 232 |
Publisher DOI: | 10.1016/j.jconrel.2012.06.019 |
PMID: | 22728515 |
Abstract: | Anti-angiogenic therapy is a potential chemotherapeutic strategy for the treatment of drug resistant cancers. However, a method for delivering such drugs to tumor endothelial cells remains to be a major impediment to the success of anti-angiogenesis therapy. We designed liposomes (LPs) with controlled diameter of around 300 nm, and modified them with a specific ligand and a cell penetrating peptide (CPP) (a dual-ligand LP) for targeting CD13-expressing neovasculature in a renal cell carcinoma (RCC). We modified the LPs with an NGR motif peptide on the top of poly(ethylene glycol) and tetra-arginine (R4) on the surface of the liposome membrane as a specific and CPP ligand, respectively. The large size prevented extravasation of the dual-ligand LP, which allowed it to associate with target vasculature. While a single modification with either the specific or CPP ligand showed no increase in targetability, the dual-ligand enhanced the amount of delivered liposomes after systemic administration to OS-RC-2 xenograft mice. The anti-tumor activity of a dual-ligand LP encapsulating doxorubicin was evaluated and the results were compared with Doxil®, which is clinically used to target tumor cells. Even though Doxil showed no anti-tumor activity, the dual-ligand LP suppressed tumor growth because the disruption of tumor vessels was efficiently induced. The comparison showed that tumor endothelial cells (TECs) were more sensitive to doxorubicin by 2 orders than RCC tumor cells, and the disruption of tumor vessels was efficiently induced. Collectively, the dual-ligand LP is promising carrier for the treatment of drug resistant RCC via the disruption of TECs. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/50278 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 畠山 浩人
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