Molecular dynamics of core-shell micelles interaction with anticancer drugs and corona proteins.

Advances in nanotechnology have given rise to various biocompatible nanomaterials, that have gained much attention in biomedical research as delivery vehicles for diagnostic and therapeutic agents. Although nanoparticles(NPs) offer many advantages, the low in vivo efficiency of existing nanocarriers is the main obstacle to their clinical translation. After exposure to the biological environment, NPs immediately interact with proteins that form protein adsorption layer called protein corona, which alters the physicochemical properties of NPs surface and further affects their biological fate. Understanding of molecular mechanisms of protein adsorption on various biological surfaces is a necessary step to improve the effectiveness of nanomedicines in vivo. In this study, we have performed molecular dynamics simulations of human serum albumin and complement C3b proteins interaction with biotin-functionalized core-shell micelles. To find out whether loading of drugs into nanoparticles affects NP surface and NP-protein interactions, we simulated nanoparticle loading with common anticancer drugs doxorubicin and paclitaxel. It was found, that initial attachment of albumin to NP surface can be triggered by both hydrophobic and electrostatic interactions, C3b anchoring relies only electrostatic interactions primarily between charged residues. NPs drug loading results in uneven distribution of drug molecules over NP surface caused by drug aggregation. However, drug clusters on NP surface did not lead to accelerated protein adsorption compared to bare NPs. These results contribute to understanding of molecular interactions on nano-bio interface towards rational design of drug delivery systems.