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

本研究旨在为高表达表皮生长因子受体(EGFR)肿瘤的抗癌药物开发一种新的给药系统。我们使用2-甲基丙烯酰氧乙基磷酰胆碱(MPC)聚合物固定的纳米粒，包括紫杉醇，与抗EGFR单抗(MAb 528)偶联。体外用四甲基偶氮唑盐比色法测定其对高表达EGFR的A431细胞和不表达EGFR的H69细胞的杀伤作用。纳米粒单独或单抗528对A431或H69均无细胞毒作用。紫杉醇对A431细胞的IC50约为10 ng/ml，与紫杉醇非偶联抗体纳米粒的IC50相近。紫杉醇单独用药组和紫杉醇非抗体偶联纳米粒的细胞毒作用无明显差异。然而，紫杉醇与单抗528偶联的纳米粒组在紫杉醇浓度较低的情况下对A431细胞的IC50值约为3.45 ng/ml(p&lt；0.001)。紫杉醇单独作用、紫杉醇非偶联纳米粒和单抗528偶联纳米粒对H69的细胞毒作用无明显差异。细胞毒作用依赖于EGFR的表达水平。这些数据表明，开发一种有效的新药物输送系统是可能的。

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.