(775e) Investigations On Permeation of Functionalized Nanoparticles Through Lipid Bilayers Using Molecular Dynamics Simulations

Understanding the properties of lipid membranes is crucial while developing drug delivery systems including liposome and other lipid-based carriers. How gold nanoparticles interact with biological membranes is of significant importance in determining the toxicity of nanoparticles as well as their potential applications in phototherapy, imaging and gene/drug delivery. It has been shown that such interactions are often determined by physicochemical factors such as size, shape, hydrophobicity and surface charge density. Surface modification of nanoparticle offers the possibility of creating site specific carriers for both drug delivery as well as diagnostic purposes. In this work, we use molecular dynamic simulations to explore the transport process of gold nanoparticles functionalized with different surface modifications through dipalmitoylphosphatidylcholine (DPPC) bilayers. A coarse-grained model was used to provide direct insight at large time and length scales. Different surface modifications such as hydrophobic, hydrophilic, or amphiphilic ligands, were applied to aid the transport of gold nanoparticles (D_{Au core} = 2~4 nm) across the lipid bilayer in order to mimic experiments. The potential of mean force profiles were obtained to give insight on how the surface modification can help the transport of the nanoparticles. The dependence on the chemical properties of the ligands, surface coverage of the ligands, and length of the ligands were investigated in our simulations. We also studied the elastic and dynamic properties of lipid bilayers during the permeation of the functionalized gold nanopaticles, which are of considerable fundamental interest. The findings described in our work will lead to better understanding of nanoparticle-lipid membrane interactions, cycotoxity and help develop more efficient nanocarrier systems for intracellular delivery of therapeutics.