Design Principles for Nanoparticles Enveloped by a Polymer-Tethered Lipid Membrane

Abstract

We propose the design for a nanoparticle carrier that combines three existing motifs into a single construct: a liposome is stabilized by anchoring it to an enclosed solid core via extended polymeric tethers that are chemically grafted to the core and physisorb into the surrounding lipid membrane. Such a design would exhibit several enticing properties, among them: (i) the anchoring stabilizes the liposome against a variety of external stresses, while preserving an aqueous compartment between core and membrane; (ii) the interplay of design parameters such as polymer length or grafting density enforces strong constraints on nanoparticle size and hence ensures a high degree of uniformity; and (iii) the physical and chemical characteristics of the individual constituents equip the construct with numerous functionalities that can be exploited in many ways. However, navigating the large parameter space requires a sound prior understanding for how various design features work together, and how this impacts potential pathways for synthesizing and assembling these nanoparticles. In this paper, we examine these connections in detail, using both soft matter theory and computer simulations at all levels of resolution. We thereby derive strong constraints on the experimentally relevant parameter space, and also propose potential equilibrium and nonequilibrium pathways for nanoparticle assembly.

Keywords: coarse-graining; drug delivery; molecular dynamics simulation; nanoparticle; theoretical modeling.