PAMAM树状大分子负载和释放阿霉素的耗散粒子动力学模拟

采用耗散粒子动力学模拟方法研究了药物输送载体聚酰胺-胺（PAMAM）树状大分子对抗癌药物阿霉素（DOX）的负载和释放行为。构建了PAMAM树状大分子的粗粒化模型，该模型能准确地重现树状大分子的构象性质。考察了PAMAM树状大分子代数（G）对DOX负载以及pH环境对DOX释放的影响。模拟结果表明，PAMAM树状大分子主要通过疏水作用将DOX包封于内部空腔，G6和G7 PAMAM树状大分子的负载能力较强，因为其孔隙率较高，内部有更多的疏水空腔。在低pH环境下，PAMAM树状大分子结构发生变化，DOX分子能快速地从其中释放，主要原因是PAMAM的伯胺、叔胺和DOX伯胺发生质子化，质子化基团间的静电排斥作用使得PAMAM树状大分子发生溶胀，导致其内部空腔暴露，促进了DOX的释放。本工作可以为基于树状大分子的药物输送体系的设计和优化提供参考。

Dissipative particle dynamics simulations on loading and release of doxorubicin by PAMAM dendrimers

Dissipative particle dynamics (DPD) simulations were employed to study the loading and release behaviors of anticancer drug doxorubicin (DOX) by drug delivery carrier polyamidoamine (PAMAM) dendrimers. A coarse-grained (CG) model for PAMAM dendrimers was first constructed, which reproduced the conformational properties of PAMAM dendrimers accurately. The effects of PAMAM dendrimer generation (G) on DOX loading and the environment pH on DOX release were investigated. Simulation results showed that PAMAM dendrimers mainly encapsulated DOX into their interior cavities through hydrophobic interaction. The encapsulation capacity of G6 and G7 PAMAM dendrimers were much better than PAMAM of lower generations, because there were more hydrophobic cavities inside G6 or G7 dendrimers for their high porosity. At low pH, PAMAM dendrimers underwent conformational changes, thus DOX molecule escaped from dendrimers quickly. Such phenomena are mainly caused by the protonation of primary amines and tertiary amines in PAMAM dendrimers and primary amines in DOX. The electrostatic repulsion between these charged groups will lead PAMAM dendrimers swelling immensely and the inner cavities being exposed, which promotes the release of DOX molecules. This work could provide useful guidance for the design and optimization of dendrimer-based drug delivery systems