| 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
|
| リソース情報 |
| ヒト・動物細胞 |
|
