文献类型：期刊文献

英文题名：Effective Therapeutic Drug Delivery by GALA3, an Endosomal Escape Peptide with Reduced Hydrophobicity

作者：Li, Chen[1];Cao, Xue-Wei[1];Zhao, Jian[1,5];Wang, Fu-Jun[2,3,4]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[2]Zhejiang Fonow Med Co Ltd, New Drug R&D Ctr, 209 West Hulian Rd, Dongyang 322100, Zhejiang, Peoples R China;[3]Shanghai R&D Ctr Standardizat Chinese Med, 1200 Cailun Rd, Shanghai 201203, Peoples R China;[4]Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, 1200 Cailun Rd, Shanghai 201203, Peoples R China;[5]East China Univ Sci & Technol, Dept Appl Biol, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2020

卷号：253

期号：2

起止页码：139

外文期刊名：JOURNAL OF MEMBRANE BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000510300700001)】；

基金：The authors declare that they have no conflict of interest regarding the conduct or outcomes of this study. This work was supported by the National Natural Science Foundation of China (Grant No. 81571795)

语种：英文

外文关键词：Endosomal escape; HBP; GALA3; BLF1

摘要：Endosomal escape is a rate-limiting step in the cytosolic delivery of therapeutic drugs. Overcoming this barrier is crucial to achieve an effective biological based therapy. In this work, we evaluated the ability of a synthetic biomimetic peptide derived from the GALA to facilitate endosomal escape of protein drugs. Our results showed that the cytoplasmic distribution of GALA fusion proteins changed according to the hydrophobicity of GALA. One of the synthetic peptides, GALA3, significantly enhanced the endosomal escape efficiency of protein drugs. The cytosolic delivery capacity of GALA3 was significantly higher than that of several previously reported endosomal escape peptides, including hemagglutinin 2 (HA2). Moreover, when GALA3 was fused to BLF1-HBP, a ribosome-inactivating protein with cell-penetrating peptide HBP, the cytotoxicity of the fusion protein was significantly increased in various cell lines, including H460, HeLa, A549, and SMCC-7721. The growth inhibition effect of GALA3-BLF1-HBP was at least 20 times greater than that of BLF1-HBP alone in different tumor cell lines. GALA3 effectively promoted the endosomal escape of BLF1-HBP in a pH-dependent manner and greatly enhanced the apoptotic activity of BLF1-HBP. Taken together, our data show that by adjusting the hydrophobicity of GALA we obtained a more effective endosomal escape peptide. Therefore, GALA3-fusions can improve the efficiency of therapeutic protein drugs.