Controlling Polymersome Surface Topology at the Nanoscale by Membrane Confined Polymer/Polymer Phase Separation

Abstract

Nature has the exquisite ability to design specific surface patterns and topologies on both the macro- and nanolength scales that relate to precise functions. Following a biomimetic approach, we have engineered fully synthetic nanoparticles that are able to self-organize their surface into controlled domains. We focused on polymeric vesicles or "polymersomes"; enclosed membranes formed via self-assembly of amphiphilic block copolymers in water. Exploiting the intrinsic thermodynamic tendency of dissimilar polymers to undergo phase separation, we mixed different vesicle-forming block copolymers in various proportions in order to obtain a wide range of polymersomes with differing surface domains. Using a combination of confocal laser scanning microscopy studies of micrometer-sized polymersomes, and electron microscopy, atomic force microscopy, and fluorescence spectroscopy on nanometer-sized polymersomes, we find that the domains exhibit similar shapes on both the micro- and nanolength scales, with dimensions that are linearly proportional to the vesicle diameter. Finally, we demonstrate that such control over the surface "patchiness" of these polymersomes determines their cell internalization kinetics for live cells.

Exploiting Endocytosis for Nanomedicines

“…Cite this article as Cold Spring Harb Perspect Biol 2013;5:a016980 the possibility to form nanoparticles with different surface topologies LoPresti et al 2011) using cell-inert and cellactive polymer domains. Nanoparticles form with either patchy or striated surface patterns (see Fig.…”

“…As shown in the graph in Figure 2C, the internalization of the patchy particles is considerably different from the pure formulations. Patchy particles with discrete domains showed substantially higher endocytosis efficiencies compared with the pure formulations across all diameters LoPresti et al 2011). More interestingly, the size effect that characterizes the pristine formulation is no longer relevant, with the patchy formulations showing a slight increase in uptake as a function of size LoPresti et al 2011).…”

“…Patchy particles with discrete domains showed substantially higher endocytosis efficiencies compared with the pure formulations across all diameters LoPresti et al 2011). More interestingly, the size effect that characterizes the pristine formulation is no longer relevant, with the patchy formulations showing a slight increase in uptake as a function of size LoPresti et al 2011). Such results show how surface topology has a quite drastic effect on cell endocytosis, possibly explaining why enveloped viruses have strong infection capability even though they come in a relatively large variety of sizes (Harris et al 2006).…”

Chemotactic synthetic vesicles: design and applications in blood brain barrier crossing

“…Furthermore, we have demonstrated (31)(32)(33)(34) that, when two different copolymers are used to form one polymersome, the resulting membrane segregates laterally into patterns whose topology is strictly controlled by the molar ratio of the two copolymers and eventually coarsen into two separate domains forming asymmetric polymersomes (35). Here, we exploit this asymmetry to achieve propulsion at the nanoscale.…”

Disk-cylinder and disk-sphere nanoparticles via a block copolymer blend solution construction

“…Alternately, one can purposely mix different block copolymers with unlike block chemistries into multi-component nanoparticles with proper kinetic processing. The limited examples of this strategy have focused on block copolymer molecules with similar molecular weights and relative block fractions for the production of blended spheres 22,23 , cylinders that contain multiple block copolymers 15,[23][24][25] and blended vesicles 26,27 .…”