Acetyl-terminated poly(amidoamine) dendrimer (G4ACE) was investigated as a pH-responsive nanocarrier for co-delivery of irinotecan (IRI) and fluorouracil (FU) using molecular dynamics simulations. The loading capacity of G4ACE at low pH is lower than that of physiological conditions. Drug molecules prefer to interact with dendrimer through conjugation on the surface monomers. The calculated Delta Gbind for G4ACE:xIRI:yFU at neutral pH is about -17.4 and -5.9 kcal.mol-1 for IRI and FU, respectively; while, the corresponding values at acidic environment are -11.8 and -2.1 kcal.mol-1, respectively. Thus, when the complex reaches the acidic environment of cancer cells, it quickly releases the bound FU molecules.
