Leaky by Design: Unlocking Polymersome Permeability Using Moderately Hydrophobic Polymer Blocks

Polymersome nanoreactors, vesicular assemblies formed from amphiphilic block copolymers, provide a versatile platform for compartmentalized catalysis and the construction of biomimetic systems. While extensive efforts have focused on the encapsulation of enzymes within such constructs, reports of vesicles displaying intrinsic membrane permeability remain unusual. Typically, selective transport across polymersome membranes requires the incorporation of channel proteins or other porogenic components. Conversely, we herein demonstrate that polymer vesicles comprising poly(butylene oxide) as the hydrophobic segment exhibit inherent permeability to small molecules without the need for artificial machineries, possibly governed by moderate hydrophobicity of this polymer and consequently hydration of the membrane. Synthesis and detailed characterization of diblock and triblock copolymers containing poly(butylene oxide) and poly(glycidol), respectively, as hydrophobic and hydrophilic blocks are first demonstrated; the self-assembly of the chains into polymer vesicles and their inherent permeability to disparate small molecules are subsequently highlighted. Notably, we further reveal that such vesicles can be conveniently loaded with a model enzyme (horseradish peroxidase), which remains entrapped in the aqueous lumen. Using a well-established colorimetric assay, we show that the vesicles are also permeable to small-enzyme substrates and products, and therefore, the reported strategy can be applied to a wide range of enzymes and functional proteins for the design of simple permeable nanoreactors for enzyme-mediated catalysis.