Smart and Selective Cancer-Killing Peptides with Cell Penetrating Sequence and Dual-Targeting Mechanism
Smart and Selective Cancer-Killing Peptides with Cell Penetrating Sequence and Dual-Targeting Mechanism
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具有细胞穿透序列和双靶向机制的智能选择性杀癌肽
DOI：
10.1016/j.colsurfa.2019.124185
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发表时间：
2020-02
期刊：
影响因子：
--
通讯作者：
Meiwen Cao
中科院分区：
文献类型：
--
作者：
Yu Wang;Jiaming Xuan;Wenjing Zhao;Zhen Ding;Lan Zhang;Rui Du;Anle Zhang;Yilin Wang;Dongxiang Li;Meiwen Cao
设计了一系列序列为Ac-RGDGPLGLAGI3GRn-NH_2(n = 4，6，8)的两亲性多肽，用于选择性杀伤肿瘤。这些分子有四个功能片段，即RGD的整合素结合片段、PLGLA的酶可切割片段、I3的疏水片段和8-精氨酸的细胞膜穿透片段。其中，含有n- = 8(RR-22)的多肽是一种高效杀灭癌细胞、对正常细胞毒性微乎其微的智能分子。对HeLa、Hpeg2和A549的半数抑制浓度分别为50 μM、41 μM和44 μM。这种高的杀癌选择性归因于双重的肿瘤靶向功能，即RGD片段与癌膜的特异性识别和结合以及肿瘤过度表达的基质金属蛋白酶-7(MMP7)对PLGLA片段的切割。这项研究说明了一种设计具有选择性和靶向性的智能治疗分子的有效策略。
A series of amphiphilic peptides with sequence of Ac-RGDGPLGLAGI3GRn-NH2(n = 4, 6, 8) have been designed for the aim of selective cancer-killing. These molecules have four functional segments, the integrin-binding segment of RGD, the enzyme-cleavable segment of PLGLA, the hydrophobic segment of I3, and the cell membrane-penetrating segment of octa-arginine. Among them, the peptide with n = 8 (RR-22) turns out to be a ‘smart’ molecule with high efficiency in killing cancer cells and negligible cytotoxicity to normal cells. The concentration causing 50% cancer cell growth inhibition (IC50) is 50 μM for HeLa, 41 μM for Hpeg2, and 44 μM for A549, respectively. The high cancer-killing selectivity is ascribed to the dual cancer-targeting function, that is, the specific recognition and binding of RGD segment to cancer membranes and the cleavage of PLGLA segment by the cancer-overexpressed matrix metalloproteinase-7 (MMP7). This study illustrates an effective strategy for designing smart therapeutic molecules with both selectivity and targeting ability.
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DOI：
10.1016/j.colsurfa.2016.07.014
发表时间：
2016
影响因子：
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影响因子：
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