Insight Into Interfacial Behaviors between Doxorubicin\nand Zwitterion/PAMAM/CQD Hybrid Nanocarrier. A Molecular Dynamics\nSimulations Study

Poly(amidoamine)\ndendrimer (PAMAM)/carbon quantum dot (CQD) nanohybrids\nare promising candidates for many biomedical applications, including\ndrug delivery. Effectively designing a hybrid nanocarrier requires\na deep understanding of the interactions of the hybrid nanoparticle\nwith the drug to ensure drug stability and therapeutic efficiency.\nIn this study, we utilized fully atomistic molecular dynamics (MD)\nsimulations to investigate the adsorption behavior of a doxorubicin\n(DOX) anticancer drug onto a zwitterion/PAMAM/CQD hybrid nanocarrier.\nThe hybrid nanoparticles were composed of CQD, at two oxidation levels,\ngrafted with PAMAM dendrimers of generation 3 (G3) or 4 (G4) decorated\nwith zwitterion monomers. Our work reveals that the generation of\nthe grafted dendrimer was the primary determinant of efficient adsorption\nof DOX, unlike the oxidation level of CQD or dendrimer surface chemistry.\nAfter grafting, the G4 dendrimers assume a more stretched conformation\ncompared to the G3 dendrimers. This allowed DOX molecules to penetrate\ninside the dendritic cavities of G4 dendrimers, resulting in enhanced\ndrug protection. The hydrophobic interaction, between the aromatic\nstructure of DOX molecules and the nonpolar parts of dendrimers, has\nbeen proven to play a crucial role in mediating the adsorption of\ndrug molecules. These findings provide valuable insights to assist\nin the design of a zwitterion/PAMAM/CQD hybrid nanoplatform for drug\ndelivery applications.