Novel Cyclic Peptides for Targeting EGFR and EGRvIII Mutation for Drug Delivery.
Novel Cyclic Peptides for Targeting EGFR and EGRvIII Mutation for Drug Delivery.
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用于靶向EGFR和EGRVIII突变的新型环状肽用于药物输送。
DOI：
10.3390/pharmaceutics14071505
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发表时间：
2022-07-20
期刊：
影响因子：
5.4
通讯作者：
Lubin, Bat Chen R.
中科院分区：
文献类型：
--
作者：
Furman, Olga;Zaporozhets, Alisa;Tobi, Dror;Bazylevich, Andrii;Firer, Michael A.;Patsenker, Leonid;Gellerman, Gary;Lubin, Bat Chen R.
表皮生长因子-表皮生长因子受体（EGF-EGFR）通路已成为选择性化疗干预的主要焦点。因此，两类EGFR抑制剂已被临床批准，即单克隆抗体和小分子激酶抑制剂。尽管对这些药物的初始反应率良好，但大多数患者会产生耐药性。因此，需要新的治疗方法。在这项工作中，我们的目标是找到一个新的EGFR特异性，短环肽，可用于靶向药物输送。将噬菌体展示肽技术和生物淘选应用于三种EGFR表达细胞，包括表达EGFRvIII突变的细胞。从内化的噬菌体提取DNA，并使用下一代测序（NGS）对肽插入物进行测序。11肽被选择用于进一步调查，使用结合，内化，和竞争测定，结果证实了共聚焦显微镜和肽对接。在这11个肽中，7个显示出特异性和选择性结合并内化到EGFR阳性（EGFR+ve）细胞中，其中两个-P6和P9-还分别显示出对非小细胞肺癌（NSCLC）和胶质母细胞瘤细胞的高特异性。这些肽与喜树碱（CPT）化学缀合。偶联物对EGFR+ve细胞的细胞毒性比游离CPT更强。我们的研究结果描述了一种新的环肽，它可以用于靶向药物输送到过表达EGFR和EGFRvIII突变的细胞。
The epidermal growth factor–epidermal growth factor receptor (EGF-EGFR) pathway has become the main focus of selective chemotherapeutic intervention. As a result, two classes of EGFR inhibitors have been clinically approved, namely monoclonal antibodies and small molecule kinase inhibitors. Despite an initial good response rate to these drugs, most patients develop drug resistance. Therefore, new treatment approaches are needed. In this work, we aimed to find a new EGFR-specific, short cyclic peptide, which could be used for targeted drug delivery. Phage display peptide technology and biopanning were applied to three EGFR expressing cells, including cells expressing the EGFRvIII mutation. DNA from the internalized phage was extracted and the peptide inserts were sequenced using next-generation sequencing (NGS). Eleven peptides were selected for further investigation using binding, internalization, and competition assays, and the results were confirmed by confocal microscopy and peptide docking. Among these eleven peptides, seven showed specific and selective binding and internalization into EGFR positive (EGFR+ve) cells, with two of them—P6 and P9—also demonstrating high specificity for non-small cell lung cancer (NSCLC) and glioblastoma cells, respectively. These peptides were chemically conjugated to camptothecin (CPT). The conjugates were more cytotoxic to EGFR+ve cells than free CPT. Our results describe a novel cyclic peptide, which can be used for targeted drug delivery to cells overexpressing the EGFR and EGFRvIII mutation.
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DOI：
10.1016/j.ijrobp.2012.10.008
发表时间：
2013-04-01
影响因子：
7
作者：
Chakravarti, Arnab;Wang, Meihua;Robins, H. Ian;Lautenschlaeger, Tim;Curran, Walter J.;Brachman, David G.;Schultz, Christopher J.;Choucair, Ali;Dolled-Filhart, Marisa;Christiansen, Jason;Gustavson, Mark;Molinaro, Annette;Mischel, Paul;Dicker, Adam P.;Bredel, Markus;Mehta, Minesh
通讯作者：
Mehta, Minesh
DOI：
10.3390/v13040649
发表时间：
2021-04-09
期刊：
Viruses
影响因子：
--
作者：
Aloisio A;Nisticò N;Mimmi S;Maisano D;Vecchio E;Fiume G;Iaccino E;Quinto I
通讯作者：
Quinto I
DOI：
10.3390/molecules20059393
发表时间：
2015-05-21
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Guo N;Jiang D;Wang L;You X;Teng YO;Yu P
通讯作者：
Yu P
影响因子：
2.3
作者：
Gellerman, Gary;Baskin, Sophia;Firer, Michael A.
通讯作者：
Firer, Michael A.
影响因子：
11.2
作者：
Emlet DR;Gupta P;Holgado-Madruga M;Del Vecchio CA;Mitra SS;Han SY;Li G;Jensen KC;Vogel H;Xu LW;Skirboll SS;Wong AJ
通讯作者：
Wong AJ