The development of a new drug delivery system using nanoparticles including paclitaxel, conjugated with anti-epidermal growth factor receptor (EGFR) monoclonal antibody.

使用包含紫杉醇在内的纳米颗粒与抗表皮生长因子受体 (EGFR) 单克隆抗体结合，开发出一种新型药物输送系统。

• 批准号: 16591353
• 负责人: HASEGAWA Hirotoshi
• 金额: $ 2.18万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591353/
• 关键词: nanoparticle; missile therapy; paclitaxel; epidermal growth factor receptor antibody; 大腸癌; CPT-11; oxaliplatin

The purpose of this study was to develop a new drug delivery system for the anticancer agent to the cancer overexpressing epidermal growth factor receptor (EGFR). We used nanoparticles immobilized with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer and including paclitaxel, conjugated with anti-EGFR monoclonal antibody (MAb 528). In vitro the cytotoxicities against the A431 cell line overexpressing the EGFR and the H69 cell line expressing no EGFR were assessed by MTT assay. Neither nanoparticles alone nor MAb 528 alone had the cytotoxicity to A431 or H69. The IC50 of paclitaxel on A431 was about 10 ng/ml, which was almost the same in the group of nanoparticles with paclitaxel non-conjugated with antibody. There were no differences in the cytotoxicity between the paclitaxel alone group and nanoparticles with paclitaxel non-conjugated with antibody. However, the IC50 on A431 was obtained with the lower concentration of paclitaxel about 3.45 ng/ml in the group of nanoparticles with paclitaxel conjugated with MAb 528 (p<0.001). There were no differences in the cytotoxicity to H69 among the paclitaxel alone, nanoparticles with paclitaxel non-conjugated and conjugated with MAb 528. The cytotoxicity was dependent on the level of the EGFR expression. These data suggested the possibility of the development of an effective, new drug deliver system.

这项研究的目的是为癌症过表达表皮生长因子受体（EGFR）的抗癌剂开发一种新的药物输送系统。我们使用了与2-甲基丙烯酰氧甲基磷酸胆碱（MPC）聚合物固定的纳米颗粒，并包括与抗EGFR单克隆抗体偶联的紫杉醇（MAB 528）。在体外，通过MTT分析评估了对EGFR过表达的A431细胞系和表达无EGFR的H69细胞系的细胞毒性。纳米颗粒均不单独或单独使用mAb 528具有A431或H69的细胞毒性。 A431上紫杉醇的IC50约为10 ng/ml，在未用抗体缀合的紫杉醇的纳米颗粒组中几乎相同。单独的紫杉醇组和纳米颗粒之间的细胞毒性没有差异，紫杉醇与抗体未缀合。然而，在与紫杉醇与MAB 528偶联的纳米颗粒组中，紫杉醇浓度较低约3.45 ng/ml，获得了A431上的IC50（p <0.001）。单独的紫杉醇，紫杉醇非偶联并与MAB 528结合的纳米颗粒之间的细胞毒性与H69没有差异。细胞毒性取决于EGFR表达的水平。这些数据表明，有效的新药传递系统开发了可能性。