論文 - 詳細
| RRC ID | 43913 |
|---|---|
| 著者 | Takara K, Hatakeyama H, Kibria G, Ohga N, Hida K, Harashima H. |
| タイトル | Size-controlled, dual-ligand modified liposomes that target the tumor vasculature show promise for use in drug-resistant cancer therapy. |
| ジャーナル | J Control Release |
| 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. |
| 巻・号 | 162(1) |
| ページ | 225-32 |
| 公開日 | 2012-8-20 |
| DOI | 10.1016/j.jconrel.2012.06.019 |
| PII | S0168-3659(12)00519-6 |
| PMID | 22728515 |
| MeSH | Animals Antibiotics, Antineoplastic / administration & dosage* Antibiotics, Antineoplastic / pharmacology Antibiotics, Antineoplastic / therapeutic use CD13 Antigens / metabolism* Cell Line, Tumor Cell-Penetrating Peptides / chemistry Cell-Penetrating Peptides / metabolism* Doxorubicin / administration & dosage* Doxorubicin / pharmacology Doxorubicin / therapeutic use Drug Delivery Systems* Drug Resistance, Neoplasm Humans Kidney / blood supply Kidney / cytology Kidney / drug effects Kidney / pathology Kidney Neoplasms / blood supply* Kidney Neoplasms / drug therapy Ligands Liposomes / chemistry Liposomes / metabolism* Male Mice Mice, Inbred BALB C Oligopeptides / chemistry Oligopeptides / metabolism Particle Size |
| IF | 7.727 |
| 引用数 | 79 |
| WOS 分野 | PHARMACOLOGY & PHARMACY CHEMISTRY, MULTIDISCIPLINARY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | OS-RC-2 |