(6ei) Computer Simulations of Nanoparticle Delivery: From Nanoparticle Design to Cell Membranes

The delivery of therapeutics to disease sites via nanocarriers represents one of the active research areas in the applications of nanotechnology to medicine. It is a rather complicated process involving several different steps ranging from the synthesis of nanocarriers with therapeutics, to the circulation of nanocarries in the body, the interactions of nanocarriers with cell surfaces, the cell membrane penetration and internalization of nanocarriers, and the release of therapeutics from the nanocarriers, etc. Each of these steps, and thus the effectiveness of the overall therapeutics delivery, are affected by different factors, such as the design of nanocarriers, the therapeutics-nanocarriers interactions, the specific composition of the disease cell surfaces and so on. Using computer simulation and modeling, we have investigated the problem from the perspectives of nanoparticles design and cell membranes: 1) the design of the functionalized spherical nanoparticles affects their specific interactions with cell surfaces of interest. Such specific interactions between the functionalized nanoparticles and cell surfaces are achieved using the ligand-receptor interactions. Different nanoparticle design factors, including the characteristics of polymer tethers, nanoparticle size, the ligand density and architectures, the ligand-receptor interaction strength, and so on, are explored in order to generalize their influences on the interaction affinity between nanoparticles and cell surfaces. The ‘dilemma’ of the interaction affinity and interaction specificity are illustrated and some strategies to overcome the ‘dilemma’ and achieve both high affinity and specificity of nanoparticles-cell surface interaction are discussed; 2) the architecture of lipid tails influences the formation and the morphologies of water pores inside the lipid membranes. The resultant formation of either hydrophobic or hydrophilic water pores inside the lipid membrane possibly dictates the transport of the materials across of lipid membranes. The knowledge gained from these studies enables the fundamental understanding of the delivery of therapeutics via nanocarries and hopefully serves as guidance for the future experimental design of nanocarriers to obtain optimal therapeutic effects.