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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。

基本信息

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

项目摘要

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.

本研究的目的是开发一种新的抗癌药物给药系统，用于过表达表皮生长因子受体（EGFR）的癌症。我们使用了用2-甲基丙烯酰氧基乙基磷酸胆碱（MPC）聚合物固定的纳米颗粒，包括与抗EGFR单克隆抗体（MAb 528）缀合的紫杉醇。MTT法检测对EGFR过表达的A431细胞株和不表达EGFR的H69细胞株的体外细胞毒作用。单独的纳米颗粒和单独的MAb 528对A431或H69都没有细胞毒性。紫杉醇对A431的IC 50约为10 ng/ml，这与紫杉醇未与抗体缀合的纳米粒组几乎相同。紫杉醇单独组和紫杉醇未与抗体偶联的纳米颗粒组之间的细胞毒性没有差异。然而，在具有与MAb 528缀合的紫杉醇的纳米颗粒组中，用约3.45 ng/ml的较低浓度的紫杉醇获得对A431的IC 50（p<0.001）。在单独的紫杉醇、具有紫杉醇非缀合物的纳米颗粒和与MAb 528缀合的纳米颗粒之间，对H69的细胞毒性没有差异。细胞毒性与EGFR表达水平有关。这些数据表明，一个有效的，新的药物输送系统的发展的可能性。