Designing Nanoparticle Trans location through Cell Membranes by Varying Amphiphilic Polymer Coatings

LY Zhang and M Becton and XQ Wang, JOURNAL OF PHYSICAL CHEMISTRY B, 119, 3786-3794 (2015).

DOI: 10.1021/acs.jpcb.5b00825

Nanoparticle (NP)-assisted drug delivery has been emerging as an active research area. Understanding and controlling the interaction of the coated NPs with cell membranes is key to the development of the efficient drug delivery technologies and to the management of nanoparticle-related health and safety issues. Cellular uptake of nanoparticles coated with mixed hydrophilic/hydrophobic polymer ligands is known to be strongly influenced by the polymer pattern on the NP surface and remains open for further exploration. To unravel the physical mechanism behind this intriguing phenomenon, here we perform dissipative particle dynamics simulations to analyze the forces and efficacy time as the copolymer-coated NPs pass through the lipid bilayer so as to provide better design of coated NPs for future drug delivery applications. Four characteristic copolymer ligands are constructed to perform the simulations: hydrophilic-hydrophobic (AB), hydrophobic- hydrophilic (BA), hydrophobic-hydrophilichydrophobichydrophilic (BABA), and a random pattern with hydrophilic and hydrophobic beads. We mainly study the critical force and potential of mean force required for entering inside of the lipid bilayer and penetration force to pass all the way through the cell membrane as well as the translocation time for these patterned NPs across the bilayer. Through copolymer ligand pattern designing, we find a suitable nanoparticle candidate with a specific polymer coating pattern for drug delivery. These findings provide useful guidelines for the molecular design of patterned NPs for controllable cell penetrability and help establish qualitative rules for the organization and optimization of copolymer ligands for desired drug delivery.

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