Enhancing tumor-specific intracellular delivering efficiency of cell-penetrating peptide by fusion with a peptide targeting to EGFR

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• 作者：Long The Nguyen ; Xu-Zhong Yang ; Xuan Du ; Jia-Wei Wang ; Rui Zhang ; Jian Zhao&#8230
• 关键词：Cell ; penetrating peptide ; Tumor ; homing peptide ; Targeted drug delivery ; Growth factor
• 刊名：Amino Acids
• 出版年：2015
• 出版时间：May 2015
• 年：2015
• 卷：47
• 期：5
• 页码：997-1006
• 全文大小：1,714 KB
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• 作者单位：Long The Nguyen (1)
  Xu-Zhong Yang (1) (2)
  Xuan Du (1)
  Jia-Wei Wang (1)
  Rui Zhang (1)
  Jian Zhao (1)
  Fu-Jun Wang (2) (3)
  Yang Dong (1)
  Peng-Fei Li (1)
  
  1. State Key Laboratory of Bioreactor Engineering, Department of Applied Biology, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China
  2. Zhejiang Reachall Pharmaceutical Co. Ltd., 209 West Hulian Road, Dongyang, 322100, Zhejiang, China
  3. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, Shanghai, China
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Analytical Chemistry
  Biochemical Engineering
  Life Sciences
  Proteomics
  Neurobiology
  
• 出版者：Springer Wien
• ISSN：1438-2199

文摘

Cell-penetrating peptides (CPPs) are well known as intracellular delivery vectors. However, unsatisfactory delivery efficiency and poor specificity are challenging barriers to CPP applications at the clinical trial stage. Here, we showed that S3, an EGFR-binding domain derived from vaccinia virus growth factor, when fused to a CPP such as HBD or TAT can substantially enhance its internalization efficiency and tumor selectivity. The uptake of S3-HBD (S3H) recombinant molecule by tumor cells was nearly 80 folds increased compared to HBD alone. By contrast, the uptake of S3H by non-neoplastic cells still remained at a low level. The specific recognition between S3 and its receptor, EGFR, as well as between HBD and heparan sulfate proteoglycans on the cell surface was essential for these improvements, suggesting a syngeneic effect between the two functional domains in conjugation. This syngeneic effect is likely similar to that of the heparin-binding epidermal growth factor, which is highly abundant particularly in metastatic tumors. The process that S3H entered cells was dependent on time, dosage, and energy, via macropinocytosis pathway. With excellent cell-penetrating efficacy and a novel tumor-targeting ability, S3H appears as a promising candidate vector for targeted anti-cancer drug delivery.