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

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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.

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Acknowledgments

This 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 “Significant New Drugs Created” of Eleventh Five-Year Plan (2009ZX09103-693).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. School of Biotechnology and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China

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

  2. School of Pharmacy and Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai, 200237, China

    Wenyun Zheng

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  1. Nanjing Lin
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  2. Wenyun Zheng
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  3. Linfeng Li
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  4. Hui Liu
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  5. Tianwen Wang
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  6. Ping Wang
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  7. Xingyuan Ma
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Corresponding author

Correspondence to Xingyuan Ma.

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Nanjing Lin and Wenyun Zheng contributed equally to this work.

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Lin, N., Zheng, W., Li, L. et al. A novel system enhancing the endosomal escapes of peptides promotes Bak BH3 peptide inducing apoptosis in lung cancer A549 cells. Targ Oncol 9, 163–170 (2014). https://doi.org/10.1007/s11523-013-0282-9

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  • DOI: https://doi.org/10.1007/s11523-013-0282-9

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