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