Gemini Lipopeptide Bearing an Ultrashort Peptide for Enhanced Transfection Efficiency and Cancer-Cell-Specific Cytotoxicity.
Gemini Lipopeptide Bearing an Ultrashort Peptide for Enhanced Transfection Efficiency and Cancer-Cell-Specific Cytotoxicity.
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DOI：
10.1021/acsomega.1c03620
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发表时间：
2021-09-07
期刊：
影响因子：
4.1
通讯作者：
Patri SV
中科院分区：
文献类型：
--
作者：
Ravula V;Lo YL;Wang LF;Patri SV
阳离子双子脂肽是一类相对较新的两亲性化合物，用于基因递送。通过将短肽与细胞穿透功能结合起来，这些脂肽可能比传统的阳离子脂质更有优势。在此，我们报道了一种用于基因传递的新型阳离子双子脂肽的设计、合成和应用。含有四个氨基酸（精氨酸-半胱氨酸-半胱氨酸-精氨酸）的超短肽作为阳离子头基，两个 α-生育酚部分作为疏水锚定基团。将新型脂肽（ATTA）掺入到传统脂质体中，其中含有不同摩尔比的1,2-二油酰-3-三甲基铵-丙烷（DOTAP）和1,2-二油酰-sn-甘油-3-磷酸乙醇胺（DOPE）。对配制的脂质体进行表征和筛选以获得更好的转染效率。来自癌性和非癌性来源的多种人类细胞系的转染活性表明，脂质体中包含最佳比例的 ATTA 可显着提高转染效率，优于传统脂质体 DOTAP-DOPE。含有 ATTA 的制剂针对多种细胞系的细胞毒性表明癌细胞系和非癌细胞系之间可能具有不同的活性。此外，含有抗癌治疗基因、编码肿瘤坏死因子相关凋亡诱导配体（pTRAIL）的质粒的ATTA制剂的脂质复合物，比常规制剂明显诱导更多的细胞毒性。结果表明，富含精氨酸的阳离子脂肽似乎是基因递送载体制剂中很有前途的成分，可提高转染效率和细胞选择性细胞毒性。
Cationic gemini lipopeptides are a relatively new class of amphiphilic compounds to be used for gene delivery. Through the possibility of incorporating short peptides with cell-penetrating functionalities, these lipopeptides may be advantageous over traditional cationic lipids. Herein, we report the design, synthesis, and application of a novel cationic gemini lipopeptide for gene delivery. An ultrashort peptide, containing four amino acids, arginine–cysteine–cysteine–arginine, serves as a cationic head group, and two α-tocopherol moieties act as hydrophobic anchoring groups. The new lipopeptide (ATTA) is incorporated into the conventional liposomes, containing 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine (DOPE), at different molar ratios. The formulated liposomes are characterized and screened for better transfection efficiency. Transfection activity in multiple human cell lines from cancerous and noncancerous origins indicates that the inclusion of an optimal ratio of ATTA in the liposomes substantially enhances the transfection efficiency, superior to that of a traditional liposome, DOTAP–DOPE. Cytotoxicity of ATTA-containing formulations against multiple cell lines indicates potentially distinct activity between cancer and noncancer cell lines. Furthermore, lipoplexes of the ATTA-containing formulations with anticancer therapeutic gene, plasmid encoding tumor necrosis factor-related apoptosis-inducing ligand (pTRAIL), induce obviously more cytotoxicity than conventional formulations. The results indicate that arginine-rich cationic lipopeptide appears to be a promising ingredient in gene delivery vector formulations to enhance transfection efficiency and cell-selective cytotoxicity.
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影响因子：
3
作者：
Domalaon, Ronald;Findlay, Brandon;Schweizer, Frank
通讯作者：
Schweizer, Frank
DOI：
10.1016/j.bbagen.2017.07.002
发表时间：
2017-09-01
影响因子：
3
作者：
Dowaidar, Moataz;Abdelhamid, Hani Nasser;Langel, Ulo
通讯作者：
Langel, Ulo
影响因子：
4.7
作者：
Jiang, Qian;Chen, Xiaobing;Gu, Zhongwei
通讯作者：
Gu, Zhongwei
影响因子：
3.7
作者：
Huang W;Seo J;Willingham SB;Czyzewski AM;Gonzalgo ML;Weissman IL;Barron AE
通讯作者：
Barron AE
影响因子：
5.2
作者：
Abdelhamid, Hani Nasser;Dowaidar, Moataz;Langel, Ulo
通讯作者：
Langel, Ulo