Acylation of the antimicrobial peptide CAMEL for cancer gene therapy.
Acylation of the antimicrobial peptide CAMEL for cancer gene therapy.
复制标题
用于癌症基因治疗的抗菌肽 CAMEL 的酰化。
DOI：
10.1080/10717544.2020.1787556
复制
发表时间：
2020-12
期刊：
影响因子：
6
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Song J;Ma P;Huang S;Wang J;Xie H;Jia B;Zhang W
获得理想的基因递送载体仍然是癌症基因治疗的主要目标。 CAMEL 是一种短的混合抗菌肽，可以通过膜裂解杀死癌细胞。在本研究中，我们通过将不同链长的脂肪酸连接到CAMEL的N端，构建了一系列非病毒载体。我们的结果表明，acyl-CAMEL 的细胞摄取和转染效率从 12 个碳的链长开始显着增加。 C18-CAMEL 被筛选用于基因传递，因为它具有最高的转染效率。令人惊讶的是，C18-CAMEL/质粒复合物通过胞吞作用进入细胞后表现出很强的内体逃逸活性。重要的是，C18-CAMEL可以将p53质粒递送至癌细胞，并通过p53的表达显着抑制细胞增殖。此外，C18-CAMEL/p53质粒复合物和MDM2抑制剂nutlin-3a对表达野生型p53的MCF-7细胞表现出显着的协同抗癌活性。最后，我们的研究表明，硬脂酸与抗菌肽的缀合是构建用于癌症基因治疗的高效且经济的非病毒载体的简单而成功的方法。
Obtaining ideal gene delivery vectors is still a major goal in cancer gene therapy. CAMEL, a short hybrid antimicrobial peptide, can kill cancer cells by membrane lysis. In this study, we constructed a series of non-viral vectors by attaching fatty acids with different chain lengths to the N-terminus of CAMEL. Our results showed that the cellular uptake and transfection efficiency of acyl-CAMEL started to significantly increase from a chain length of 12 carbons. C18-CAMEL was screened for gene delivery because it had the highest transfection efficiency. Surprisingly, C18-CAMEL/plasmid complexes displayed strong endosomal escape activity after entering cells via endocytosis. Importantly, C18-CAMEL could deliver p53 plasmids to cancer cells and significantly inhibited cell proliferation by the expression of p53. In addition, the C18-CAMEL/p53 plasmid complexes and the MDM2 inhibitor nutlin-3a showed significantly synergistic anticancer activity against MCF-7 cells expressing wild-type p53. Conclusively, our study demonstrated that conjugation of stearic acid to antimicrobial peptides is a simple and successful approach for constructing efficient and economical non-viral vectors for cancer gene therapy.
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DOI：
10.1016/j.jconrel.2013.08.300
发表时间：
2013-12-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Kullberg M;McCarthy R;Anchordoquy TJ
通讯作者：
Anchordoquy TJ
影响因子：
5.1
作者：
Dash, PR;Read, ML;Seymour, LW
通讯作者：
Seymour, LW
影响因子：
10.8
作者：
Katayama, Sayaka;Hirose, Hisaaki;Futaki, Shiroh
通讯作者：
Futaki, Shiroh
影响因子：
16.1
作者：
Boisguérin P;Deshayes S;Gait MJ;O'Donovan L;Godfrey C;Betts CA;Wood MJ;Lebleu B
通讯作者：
Lebleu B
影响因子：
17.3
作者：
Hill AB;Chen M;Chen CK;Pfeifer BA;Jones CH
通讯作者：
Jones CH