College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530200, China; Key Laboratory of Common Technology of Chinese Medicine Preparations, Guangxi University of Chinese Medicine, Nanning 530200, China.
Qingdao Jimo District People's Hospital, Qingdao 266228, China.
J Control Release. 2022 Sep;349:592-605. doi: 10.1016/j.jconrel.2022.07.018. Epub 2022 Jul 22.
Abnormal regulation of cell signaling pathways on cell survival, proliferation and migration contributes to the development of malignant tumors. Among them, epidermal growth factor receptor (EGFR) is one of the most important biomarkers in many types of malignant solid tumors. Its over-expression and mutation status can be served as a biomarker to identify patients who can be benifit from EGFR tyrosine kinase inhibitors and anti-EGFR monocloncal antibody (mAb) therapy. For decades, researches on EGFR targeted ligands were actively carried out to identify potent candidates for cancer therapy. An ideal EGFR ligand can competitively inhibit the binding of endogenous growth factor, such as epidermal growth factor (EGF) and transforming growth factor-α(TGF-α) to EGFR, thus block EGFR signaling pathway and downregulate EGFR expression. Alternatively, conjugation of EGFR ligands on drug delivery systems (DDS) can facilitate targeting delivery of therapeutics or diagnostic agents to EGFR over-expression tumors via EGFR-mediated endocytosis. GE11 peptide is one of the potent EGFR ligand screened from a phage display peptide library. It is a dodecapeptide that can specifically binds to EGFR with high affinity and selectivity. GE11 has been widely used in the diagnosis and targeted delivery of drugs for radiotherapy, genetherapy and chemotherpy against EGFR positive tumors. In this review, the critical factors affecting the in vivo and in vitro targeting performance of GE11 peptide, including ligand-receptor intermolecular force, linker bond properties and physiochemical properties of carrier materials, are detailedly interpreted. This review provides a valuable vision for the rational design and optimization of GE11-based active targeting strategies for cancer treatment, and it will promote the translation studies of GE11 from lab research to clinical application.
细胞信号通路的异常调节对细胞的存活、增殖和迁移有重要影响，从而导致恶性肿瘤的发生。其中，表皮生长因子受体（EGFR）是许多类型恶性实体瘤中最重要的生物标志物之一。其过表达和突变状态可作为生物标志物，以识别能够从 EGFR 酪氨酸激酶抑制剂和抗 EGFR 单克隆抗体（mAb）治疗中获益的患者。几十年来，人们积极开展针对 EGFR 靶向配体的研究，以鉴定用于癌症治疗的有效候选物。理想的 EGFR 配体可以竞争性抑制内源性生长因子（如表皮生长因子（EGF）和转化生长因子-α（TGF-α））与 EGFR 的结合，从而阻断 EGFR 信号通路并下调 EGFR 表达。或者，将 EGFR 配体缀合到药物递送系统（DDS）上，可以通过 EGFR 介导的内吞作用，促进治疗剂或诊断剂靶向递送至 EGFR 过表达的肿瘤。GE11 肽是从噬菌体展示肽文库中筛选出的一种有效的 EGFR 配体。它是一种十二肽，能够与 EGFR 特异性结合，具有高亲和力和选择性。GE11 已广泛用于 EGFR 阳性肿瘤的放射治疗、基因治疗和化学治疗的诊断和靶向药物递送。本文详细解释了影响 GE11 肽体内外靶向性能的关键因素，包括配体-受体分子间力、连接子键特性和载体材料的物理化学性质。本文为基于 GE11 的主动靶向策略的合理设计和优化提供了有价值的视角，以促进 GE11 从实验室研究向临床应用的转化研究。
