Designing Nanoparticle Translocation through Cell Membranes by Varying Amphiphilic Polymer Coatings

Abstract

Nanoparticle-assisted drug delivery has been emerging as an active research area. Understanding and controlling the interaction of the coated-nanoparticles (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), and hydrophobic-hydrophilichydrophobic-hydrophilic (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 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 copolymers ligands for desired drug delivery.

Effects of nanobubble collapse on cell membrane integrity

“…The standard values σ = 3.0 and γ = 4.5 are used in our study [Zhang et al , 2015; Zhang and Wang, 2015a; 2015b]. The mass, length and time scales are all normalized in the DPD simulations, with the unit of length taken to be the cutoff radius r c , the unit of mass to be that of the solvent beads, and the unit of energy to be k B T .…”

Facile synthesis of wormlike quantum dots-encapsulated nanoparticles and their controlled surface functionalization for effective bioapplications

“…As illustrated in several studies, the size, shape, and surface functional groups of nanoparticles can significantly influence their behaviors in biological systems [12,13]. Our recent investigation revealed that silica and gold nanoparticles with bigger aspect ratios were taken up by cells in larger amounts and had greater impact on gene transfection performance [14,15].…”

Trigger-Responsive Gene Transporters for Anticancer Therapy

“…Mishra et al showed that human immunodeficiency virus (HIV) transactivator (TAT) peptide conjugated to a small cargo can easily translocate through the membrane via forming a membrane pore, but if the cargo is of a few nanometer size more, then it will bind to the cell membrane and eventually get internalized via the endocytic pathway [25]. In order to develop GTs following non-endocytic pathway, certain criteria have to be followed such as large size, amphiphilicity, and anionic nature [26,27,28,29]. Above all, it is quite necessary to study the non-endocytic pathway in more detail and it is possible by using computational tools, fluorescent probes, and cut through techniques to know the in depth nature of the cell membrane penetration of GTs.…”