title: A novel system enhancing the endosomal escapes of peptides promotes Bak BH3 peptide inducing apoptosis in lung cancer A549 cells.
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.
authors.affiliation: School of Biotechnology and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Nanjing
authors.initials: N
authors.lastname: Lin
authors.forename: Wenyun
authors.initials: W
authors.lastname: Zheng
authors.forename: Linfeng
authors.initials: L
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Tianwen
authors.initials: T
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Ma
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D010446:Peptide Fragments / Q000008:administration & dosage*; D010455:Peptides / Q000008:administration & dosage; D011518:Proto-Oncogene Proteins / Q000008:administration & dosage*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D025801:Ubiquitin / Q000008:administration & dosage; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; C474007:Bax protein (53-86); C526981:INF7 peptide; D010446:Peptide Fragments; D010455:Peptides; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D025801:Ubiquitin; D054322:tat Gene Products, Human Immunodeficiency Virus