Antitumor activity of a folate receptor-targeted immunoglobulin G-doxorubicin conjugate.
Antitumor activity of a folate receptor-targeted immunoglobulin G-doxorubicin conjugate.
复制标题
叶酸受体靶向免疫球蛋白 G-阿霉素缀合物的抗肿瘤活性
DOI：
10.2147/ijn.s125591
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发表时间：
2017
影响因子：
8
通讯作者：
Xiang G
中科院分区：
文献类型：
--
作者：
Yang T;Xu L;Li B;Li W;Ma X;Fan L;Lee RJ;Xu C;Xiang G
抗体药物偶联物（ADC）的开发是一种有前景的癌症治疗策略。在这项研究中，叶酸通过聚乙二醇 (PEG) 连接体与免疫球蛋白 G (IgG) 缀合，免疫球蛋白 G (IgG) 与阿霉素 (DOX) 连接，形成新型 ADC 叶酸-PEG-IgG-DOX (FA-PEG-IgG-DOX)。 FA-PEG-IgG-DOX 在 HeLa 和 KB 细胞中表现出较高的靶向效率，与 IgG-DOX 相比，DOX 的摄取和保留显着提高约 10 倍。随后，在 HeLa 和 KB 细胞中，FA-PEG-IgG-DOX 的抗肿瘤活性比 IgG-DOX 高至少 8 倍，并且在这些细胞中诱导的细胞凋亡也比 IgG-DOX 多。此外，FA-PEG-IgG-DOX的循环时间比FA-IgG-DOX长2倍，但并没有增加DOX在小鼠心脏中的分布。重要的是，FA-PEG-IgG-DOX 治疗显着抑制异种移植小鼠的肿瘤生长。总之，我们的结果表明 FA-PEG-IgG 是用于递送化疗药物的有效 ADC 载体，并且将肿瘤靶向配体与抗体缀合是生产 ADC 药物的有前途的策略。
Development of antibody-drug conjugates (ADCs) is a promising therapeutic strategy for cancer therapy. In this study, folate was conjugated via a polyethyleneglycol (PEG) linker to immunoglobulin G (IgG), which was linked to doxorubicin (DOX), to form a novel ADC folate-PEG-IgG-DOX (FA-PEG-IgG-DOX). The FA-PEG-IgG-DOX showed high targeting efficiency in HeLa and KB cells and significantly improved the uptake and retention of DOX compared with IgG-DOX about 10-fold. Subsequently, FA-PEG-IgG-DOX was shown to have at least 8 times higher antitumor activity than IgG-DOX both in HeLa and KB cells and also induced more apoptosis in those cells than IgG-DOX. Moreover, FA-PEG-IgG-DOX had a 2 times longer circulating time than FA-IgG-DOX, but did not increase the DOX distribution in mouse hearts. Importantly, FA-PEG-IgG-DOX treatment significantly inhibited tumor growth in xenograft mice. Together, our results indicate that FA-PEG-IgG is an effective ADC carrier for delivery of chemotherapeutic agents and that conjugating tumor targeting ligands to antibodies is a promising strategy for producing ADC drugs.