Insight Into Interfacial Behaviors between Doxorubicin and Zwitterion/PAMAM/CQD Hybrid Nanocarrier. A Molecular Dynamics Simulations Study.

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