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

本研究的目的是开发一种新的抗癌药物给药系统，用于肿瘤过表达的表皮生长因子受体（EGFR）。我们使用2-甲基丙烯酰氧乙基磷酸胆碱（MPC）聚合物固定纳米颗粒，包括紫杉醇，偶联抗egfr单克隆抗体（MAb 528）。在体外用MTT法评价过表达EGFR的A431细胞株和不表达EGFR的H69细胞株的细胞毒性。纳米颗粒单独或MAb 528单独对A431或H69都没有细胞毒性。紫杉醇对A431的IC50约为10 ng/ml，与未偶联紫杉醇的纳米颗粒组基本相同。紫杉醇单药组与紫杉醇非偶联抗体纳米颗粒组细胞毒性无差异。而在紫杉醇与MAb 528偶联的纳米颗粒组中，紫杉醇浓度较低，对A431的IC50为3.45 ng/ml （p<0.001）。紫杉醇单药、紫杉醇非偶联纳米粒子和与MAb 528偶联纳米粒子对H69的细胞毒性没有差异。细胞毒性与EGFR表达水平有关。这些数据表明了开发一种有效的新型药物输送系统的可能性。

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.