Improvement of stability and efficacy of c16y therapeutic peptide via molecular self-assembly into tumor-responsive nanoformulation
文献类型：期刊论文
| 作者 | Ding, Yanping1; Ji, Tianjiao1; Zhao, Ying1; Zhang, Yinlong1; Zhao, Xiaozheng1; Zhao, Ruifang1; Lang, Jiayan1; Zhao, Xiao1; Shi, Jian1; Sukumar, Saraswati2 |
| 刊名 | Molecular cancer therapeutics
 |
| 出版日期 | 2015-10-01 |
| 卷号 | 14期号:10页码:2390-2400 |
| ISSN号 | 1535-7163 |
| DOI | 10.1158/1535-7163.mct-15-0484 |
| 通讯作者 | Nie, guangjun(niegj@nanoctr.cn) |
| 英文摘要 | Peptide therapeutics hold great promise for the treatment of cancer due to low toxicity, high specificity, and ease of synthesis and modification. however, the unfavorable pharmacokinetic parameters strictly limit their therapeutic efficacy and clinical translation. here, we tailor-designed an amphiphilic chimeric peptide through conjugation of functional 3-diethylaminopropyl isothiocyanate (deap) molecules to a short antitumor peptide, c16y. the ultimate deap-c16y peptides self-assembled into spherical nanostructures at physiologic conditions, which dissociated to release individual peptide molecules in weakly acidic tumors. deap-c16y peptides showed negligible cytotoxicity but impaired vascular endothelial cell migration and tubule formation by inactivation of the focal adhesion kinase and pi3k-akt pathways, as well as tumor cell invasion by decreasing invadopodia formation. compared with c16y, the systemically administered deap-c16y nanostructures exhibited superior stability, thereby allowing prolonged treatment interval and resulting in significant decreases in microvessel density, tumor growth, and distant metastasis formation in orthotopic mammary tumormodels. through encapsulation of hydrophobic doxorubicin, deap-c16y nanostructure served as a smart carrier to achieve targeted drug delivery and combination therapy. our study, for the first time, demonstrates that a simple nanoformulation using a functional antitumor peptide as the building block can show innate antitumor activity and also provide a nanoplatform for combination therapy, opening a new avenue for the design of antitumor nanotherapeutics. (c) 2015 aacr. |
| WOS关键词 | CYTOTOXIC PEPTIDE ; DRUG CARRIER ; CANCER ; ANGIOGENESIS ; NANOPARTICLES ; INVADOPODIA ; DELIVERY ; NANOSTRUCTURES ; TRANSLOCATION ; AMPHIPHILES |
| WOS研究方向 | Oncology |
| WOS类目 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000363405600023 |
| 出版者 | AMER ASSOC CANCER RESEARCH |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2176473 |
| 专题 | 高能物理研究所 |
| 通讯作者 | Nie, Guangjun |
| 作者单位 | 1.Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China 2.Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA |
| 推荐引用方式 GB/T 7714 | Ding, Yanping,Ji, Tianjiao,Zhao, Ying,et al. Improvement of stability and efficacy of c16y therapeutic peptide via molecular self-assembly into tumor-responsive nanoformulation[J]. Molecular cancer therapeutics,2015,14(10):2390-2400. |
| APA | Ding, Yanping.,Ji, Tianjiao.,Zhao, Ying.,Zhang, Yinlong.,Zhao, Xiaozheng.,...&Nie, Guangjun.(2015).Improvement of stability and efficacy of c16y therapeutic peptide via molecular self-assembly into tumor-responsive nanoformulation.Molecular cancer therapeutics,14(10),2390-2400. |
| MLA | Ding, Yanping,et al."Improvement of stability and efficacy of c16y therapeutic peptide via molecular self-assembly into tumor-responsive nanoformulation".Molecular cancer therapeutics 14.10(2015):2390-2400. |
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