4.8 Article

Enzyme-responsive peptide dendrimer-gemcitabine conjugate as a controlled-release drug delivery vehicle with enhanced antitumor efficacy

期刊

ACTA BIOMATERIALIA
卷 55, 期 -, 页码 153-162

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2017.02.047

关键词

Nanoscale; Drug delivery; Peptide dendrimer; Antitumor efficacy

资金

  1. International Science and Technology Cooperation Program of China (ISTCP) [2015DFE52780]
  2. National Natural Science Foundation of China [51373104, 81361140343, 51673127, 81621003, 81273507]
  3. Joint Sino-German Research Project [GZ905]

向作者/读者索取更多资源

Stimuli-responsive peptide dendrimer-drug conjugates have presented significant potential for cancer therapy. To develop an effective nanoscale chemotherapeutic prodrug, we developed a novel enzyme-responsive PEGylated lysine peptide dendrimer-gemcitabine conjugate (Dendrimer-GEM) based nanoparticle via the highly efficient click reaction. Owing to the glycyl phenylalanyl leucyl glycine tetra-peptide (GFLG) as an enzyme-cleavable linker to conjugate gemcitabine (GEM), the prepared nanoparticles were able to release drug significantly faster in the tumor cellular environments, which specifically contains secreted Cathepsin B, quantifiably more than 80% GEM was released with Cathepsin B compared to the condition without Cathepsin B at 24 h. This nanoparticle demonstrated enhanced antitumor efficacy in a 4T1 murine breast cancer model without obvious systemic toxicity, resulting in significantly suppressed relative tumor volumes (86.17 +/- 38.27%) and a 2-fold higher value of tumor growth inhibition (similar to 90%) than GEM center dot HCl treatment. These results suggest that the PEGylated peptide dendrimer-gemcitabine conjugate can be an effective antitumor agent for breast cancer therapy. Statement of Significance We found that the functionalized dendrimer based nanoscale drug delivery vehicles exhibited enhanced therapeutic indexes and reduced toxicity as compared to the free drug gemcitabine. Compared with current nanoparticles, such as dendritic anticancer drug delivery systems, the new design was capable of self-assembling into nanoscale particles with sizes of about 80-110 nm, which is suitable as antitumor drug delivery vehicle due to the potential longer intravascular half-life and higher accumulation in tumor tissue via EPR effect. Owing to the optimized architecture, the system was given the enzyme-responsive drug release feature, and showed excellent antitumor activity on the 4T1 breast tumor model due to the evidences from tumor growth curves, immunohistochemical analysis and confocal laser scanning microscopy. Meanwhile, no significant side effect was observed by histological analysis. This study demonstrated that PEGylated peptide dendritic architecture may be used as efficient and safe nanoscale drug delivery vehicle for cancer therapy. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据