西妥昔单抗
表皮生长因子受体
癌症研究
聚合物囊泡
细胞毒性
靶向治疗
乳腺癌
肺癌
化疗
表皮生长因子受体抑制剂
单克隆抗体
化学
癌症
医学
抗体
肿瘤科
内科学
免疫学
体外
生物化学
共聚物
两亲性
聚合物
有机化学
作者
Shujing Yue,Yifan Zhang,Yaohua Wei,Rainer Haag,Huanli Sun,Zhiyuan Zhong
出处
期刊:Biomacromolecules
[American Chemical Society]
日期:2021-12-16
卷期号:23 (1): 100-111
被引量:3
标识
DOI:10.1021/acs.biomac.1c01065
摘要
Targeted nanomedicines particularly armed with monoclonal antibodies are considered to be the most promising advanced chemotherapy for malignant cancers; however, their development is hindered by their instability and drug leakage problems. Herein, we constructed a robust cetuximab-polymersome-mertansine nanodrug (C-P-DM1) for highly potent and targeted therapy of epidermal growth factor receptor (EGFR)-positive solid tumors. C-P-DM1 with a tailored cetuximab surface density of 2 per P-DM1 exhibited a size of ca. 60 nm, high stability with minimum DM1 leakage, glutathione-triggered release of native DM1, and 6.0-11.3-fold stronger cytotoxicity in EGFR-positive human breast (MDA-MB-231), lung (A549), and liver (SMMC-7721) cancer cells (IC50 = 27.1-135.5 nM) than P-DM1 control. Notably, intravenous injection of C-P-DM1 effectively repressed subcutaneous MDA-MB-231 breast cancer and orthotopic A549-Luc lung carcinoma in mice without inducing toxic effects. Strikingly, intratumoral injection of C-P-DM1 completely cured 60% of mice bearing breast tumor without recurrence. This robust cetuximab-polymersome-mertansine nanodrug provides a promising new strategy for targeted treatment of EGFR-positive solid malignancies.
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