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 language | English (US) |
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Pages (from-to) | 163-170 |
Number of pages | 8 |
Journal | Targeted Oncology |
Volume | 9 |
Issue number | 2 |
DOIs | |
State | Published - 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