A novel system enhancing the endosomal escapes of peptides promotes Bak BH3 peptide inducing apoptosis in lung cancer A549 cells

Nanjing Lin, Wenyun Zheng, Linfeng Li, Hui Liu, Tianwen Wang, Ping Wang, Xingyuan Ma

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Therapeutic peptides have been proven useful for treating various diseases. However, it is difficult for therapeutic peptides to reach their target sites with an effective concentration due to inefficient intracellular delivery. Although Tat transduction peptide is a promising tool to deliver therapeutic peptides into cells, the entrapment within endosomes and the nuclear localization of Tat transduction peptide severely limited the biological effects of Tat-linked cargos. In this study, we designed a novel peptide delivering system, Tat-INF7-ubiquitin (TIU), which consisted of Tat transduction peptide, endosomal escape enhancer peptide INF7, and ubiquitin protein. We found that the TIU system was able to efficiently deliver the mCherry fluorescent proteins and the apoptosis-inducing Bak BH3 peptide into the cytosol. The Bak BH3 peptide transported into the cells by the TIU system increased the apoptotic rate to 46.15±4.86 % (p<0.001) in A549 cells, while Tat-BH3 could result in only 20.45±2.89 %. These results demonstrated that the TIU system could enhance the effects of therapeutic peptides by facilitating the transmembrane delivery of peptides into the cells and the escape of target proteins from the endosome efficiently.

Original languageEnglish (US)
Pages (from-to)163-170
Number of pages8
JournalTargeted Oncology
Volume9
Issue number2
DOIs
StatePublished - Jun 2014

Bibliographical note

Funding Information:
AcknowledgmentsThis work was supported by Key grant cultivating the project and interdiscipline of the Chinese Education Ministry, partially supported by the Open Funding Project of the State Key Laboratory of Bioreactor Engineering and the National Natural Science Foundation (30873190) and the National Science Research Project

Keywords

  • Bak BH3
  • Cytosolic delivery
  • Inducing apoptosis
  • Tat-INF7-ubiquitin (TIU) system

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