Tailoring Macromolecular Expression at Polymersome Surfaces

Abstract A series of amphiphilic ABC triblock copolymers are synthesized by atom transfer radical polymerization, wherein the ‘A’ and ‘C’ blocks are hydrophilic and the pH‐sensitive ‘B’ block can be switched from hydrophilic in acidic solution to hydrophobic at pH 7. Careful addition of base to the molecularly dissolved copolymer in acidic solution readily induces the self‐assembly of such triblock copolymers at around neutral pH to form pH‐sensitive polymersomes (a.k.a. vesicles) with asymmetric membranes. By systematic variation of the relative volume fractions of the ‘A’ and ‘C’ blocks, the chemical nature of the polymer chains expressed at the interior or exterior corona of the polymersomes can be selected. Treatment of primary human dermal fibroblast cells with these asymmetric polymersomes demonstrates the biological consequences of such spatial segregation, with both polymersome cytotoxicity and endocytosis rates being dictated by the nature of the polymersome surface chemistry. The pH‐sensitive nature of the polymersomes readily facilitates their dissociation after endocytosis due to the relatively low endosomal pH, which results in the rapid release of an encapsulated dye. Selective binding of anionic substrates such as DNA within the inner cationic polymersome volume, coupled with a biocompatible exterior, leads to potential gene delivery applications for these pH‐sensitive asymmetric nanovectors.