文献研究指出药物最终能否到达靶细胞器完全由药物载体决定，阐明药物载体在细胞内的去向问题，对药物发挥疗效起到至关重要的作用。目前聚酰胺-胺树状大分子（PAMAM）细胞内最终去向还不清楚。我们的前期研究显示PAMAM在肿瘤细胞内存在外排现象并且其表面电荷可能会影响外排。为阐明PAMAM的肿瘤细胞外排机制和表面电荷对其外排的影响，本课题使用代数相同、结构相同、表面电荷不同的PAMAM-NH2（带正电）、PAMAM-OH（不带电）和PAMAM-COOH（带负电），创新性地开展外排相关作用规律（外排动力学和外排途径）及其机制（细胞周期、亚细胞器膜蛋白和多药耐药膜蛋白）的研究；然后使用更多表面带电荷载体，针对以上内容进行验证性实验，总结出表面电荷对药物载体外排的影响规律；最后考察载药PAMAM细胞外排动力学，并与空白PAMAM相比较。为一大类表面带电荷药物载体应用于抗肿瘤治疗时的设计提供新的理论指导。

The drug carriers will determiine weather drugs could reach the target organelles. Thus, it is important to clarify the intracellular fate of the drug carriers. To date, the final destination of PAMAM in tumor cells is not clear. Our previous research has shown that the PAMAM can be excreted by tumor cells and the surface charges influence its exocytosis. To explore the exocytosis mechanism and the effect of surface charge on exocytosis, this study was divided into three parts as below. Firstly, using PAMAM-NH2 with positively charged surface, PAMAM-OH with no charge on the surface and PAMAM-COOH with negatively charged surface to carry out the innovative research on the exocytosis dynamics, exocytosis pathways and the exocytosis mechanism of the PAMAM. This study illuminated the exocytosis mechanism in terms of cell cycle, organelle membrane protein and ATP binding cassette proteins. Secondly, to summarize the law that the effect of surface charge on the exocytosis, we ran the same experiments about exocytosis using more drug carriers with charges on the surface. Finally, PAMAM/DOX was prepared. The exocytosis dynamics of PAMAM/DOX was evaluated and compared with the PAMAM. Our aim was to support the rational design of drug carriers with charge on the surface to obtain the better anti-tumor activity.