論文 - 詳細
| RRC ID | 44413 |
|---|---|
| 著者 | Kibria G, Hatakeyama H, Ohga N, Hida K, Harashima H. |
| タイトル | The effect of liposomal size on the targeted delivery of doxorubicin to Integrin αvβ3-expressing tumor endothelial cells. |
| ジャーナル | Biomaterials |
| Abstract |
Size of the liposomes (LPs) specially governs its biodistribution. In this study, LPs were developed with controlled sizes, where variation in LP size dictates the ligand-receptor interaction, cellular internalization and its distribution within the tumor microenvironment. The therapeutic efficacies of doxorubicin (DOX)-loaded RGD modified small size (~100 nm in diameter, dnm) and large size (~300 dnm) PEGylated LPs (RGD-PEG-LPs) were compared to that of Doxil (a clinically used DOX-loaded PEG-LP, ~100 dnm) in DOX resistant OSRC-2 (Renal cell carcinoma, RCC) tumor xenografts. Doxil, which accumulated in tumor tissue via the enhanced permeability and retention (EPR) effect, failed to suppress tumor growth. Small size RGD-PEG-LP, that targets the tumor endothelial cells (TECs) and extravasates to tumor cells, failed to provide anti-tumor effect. Large size RGD-PEG-LP preferentially targets the TECs via minimization of the EPR effect, and significantly reduced the tumor growth, which was exerted through its strong anti-angiogenic activity on the tumor vasculature rather than having a direct effect on DOX resistant RCC. The prepared large size RGD-PEG-LP that targets the TECs via interacting with Integrin αvβ3, is a potentially effective and alternate therapeutic strategy for the treatment of DOX resistant tumor cells by utilizing DOX, in cases where Doxil is ineffective. |
| 巻・号 | 34(22) |
| ページ | 5617-27 |
| 公開日 | 2013-7-1 |
| DOI | 10.1016/j.biomaterials.2013.03.094 |
| PII | S0142-9612(13)00428-6 |
| PMID | 23623323 |
| MeSH | Animals Antineoplastic Agents / pharmacology Antineoplastic Agents / therapeutic use Cell Death / drug effects Cell Line, Tumor Cell Shape / drug effects Doxorubicin / pharmacology Doxorubicin / therapeutic use* Drug Delivery Systems* Drug Resistance, Neoplasm / drug effects Endocytosis / drug effects Endothelial Cells / drug effects Endothelial Cells / metabolism* Humans Integrin alphaVbeta3 / metabolism* Liposomes / chemistry* Male Mice Mice, Inbred BALB C Neoplasms / blood supply Neoplasms / drug therapy* Neoplasms / metabolism Neoplasms / pathology Oligopeptides / pharmacology Organ Specificity / drug effects Particle Size* Polyethylene Glycols / chemistry Tissue Distribution / drug effects |
| IF | 10.317 |
| 引用数 | 57 |
| WOS 分野 | ENGINEERING, BIOMEDICAL MATERIALS SCIENCE, BIOMATERIALS |
| 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 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | OS-RC-2(RCB0735) |