Tumor penetrability and anti-angiogenesis using iRGD-mediated delivery of doxorubicin-polymer conjugates
文献类型：期刊论文
| 作者 | Wang, Ke1; Zhang, Xiaofeng1; Liu, Yang2,3; Liu, Chang1; Jiang, Baohong3 ; Jiang, Yanyan1
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| 刊名 | BIOMATERIALS
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| 出版日期 | 2014-10 |
| 卷号 | 35期号:30页码:8735-8747 |
| ISSN号 | 0142-9612 |
| 关键词 | Tumor-penetrating peptide iRGD Tumor vascular permeability Co-administration Conjugates |
| DOI | 10.1016/j.biomaterials.2014.06.042 |
| 文献子类 | Article |
| 英文摘要 | Tumor-penetrating peptide, iRGD (internalizing RGD, CRGDK/RGPD/EC) with the similar affinity to alpha v integrins as conventional RGD cyclopeptide could enhance the tumor penetrability of drugs by binding to neuropilin-1 (NRP-1) that over-expressed on both angiogenic blood vessels and tumor cells. Comparing with our previous study, in which a RGD cyclopeptide (RGDyC) was bound to PEGylated polyamidoamine (PAMAM) dendrimer with doxorubicin (DOX) by acid-sensitive cis-aconityl linkage (PEG-PAMAM-cis-aconityl-DOX, PPCD), the present study selected iRGD instead of previous RGD to produce iRGD-PPCD conjugate. The effect of iRGD-mediated PPCD on tumor penetration was compared with the conventional RGD ones via administration of RGDs-modified PPCD (iRGD/RGDs-PPCD) and co-administration of RGDs and PPCD (iRGD/RGD + PPCD). C6 cells were selected as the cell model owing to the highest expression of av integrins and NRP-1 among four tumor cell lines. In vitro cytotoxicity and cellular uptake showed no significant difference between RGD-PPCD and iRGD-PPCD, but glioma spheroid penetration study showed that RGD-PPCD, iRGD-PPCD and iRGD + PPCD penetrated into C6 spheroids with a depth of 115 gm, 144 gm and 150 gm, respectively, indicating that the iRGD-mediated PPCD delivery system had a stronger penetrating ability than the RGD ones. In vivo results also demonstrated the superiority of iRGD system over RGD ones. After systemic administration, iRGD-mediated PPCD increased tumor vascular permeability, decreased tumor vascular density and average vascular diameter. Correspondingly, the iRGD system exhibited stronger penetration ability, higher accumulation in brain tumor. The median survival time of iRGD + PPCD, iRGD-PPCD and RGD-PPCD treatment groups were 61, 57.5 and 43.5 days. The present findings strongly suggested that the iRGD-mediated drug delivery system could significantly improve the efficacy of tumor therapy through enhancing tumor accumulation and penetration as compared to the conventional RGD ones. (C) 2014 Elsevier Ltd. All rights reserved. |
| WOS关键词 | IN-VIVO ; VASCULAR NORMALIZATION ; ANTITUMOR-ACTIVITY ; CANCER ; NANOPARTICLES ; THERAPY ; PEPTIDE ; GLIOMA ; VITRO ; PENETRATION |
| 资助项目 | National Key Basic Research Program of China[2013CB932502] ; National Natural Science Foundation of China[81172185] |
| WOS研究方向 | Engineering ; Materials Science |
| 语种 | 英语 |
| 出版者 | ELSEVIER SCI LTD |
| WOS记录号 | WOS:000340849600027 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276892]  |
| 专题 | 上海中药现代化研究中心 |
| 通讯作者 | Jiang, Yanyan |
| 作者单位 | 1.Fudan Univ, Sch Pharm, Minist Educ, Key Lab Smart Drug Delivery, Shanghai 201203, Peoples R China; 2.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Cardiovasc Surg, Shanghai 200127, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wang, Ke,Zhang, Xiaofeng,Liu, Yang,et al. Tumor penetrability and anti-angiogenesis using iRGD-mediated delivery of doxorubicin-polymer conjugates[J]. BIOMATERIALS,2014,35(30):8735-8747. |
| APA | Wang, Ke,Zhang, Xiaofeng,Liu, Yang,Liu, Chang,Jiang, Baohong,&Jiang, Yanyan.(2014).Tumor penetrability and anti-angiogenesis using iRGD-mediated delivery of doxorubicin-polymer conjugates.BIOMATERIALS,35(30),8735-8747. |
| MLA | Wang, Ke,et al."Tumor penetrability and anti-angiogenesis using iRGD-mediated delivery of doxorubicin-polymer conjugates".BIOMATERIALS 35.30(2014):8735-8747. |
入库方式： OAI收割
来源：上海药物研究所
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