It is well-known that polymerization-induced self-assembly (PISA) enables the efficient preparation of a wide range of block copolymer nano-objects. For example, the RAFT aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) using zwitterionic poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC) or non-ionic poly(ethylene glycol) (PEG) precursors produces spheres, worms or vesicles, depending on the precise reaction conditions. Similarly, relatively small vesicles with narrow size distributions can be prepared using a pair of long and short poly(methacrylic acid) precursors for the RAFT dispersion polymerization of benzyl methacrylate in ethanol. Herein we seek to integrate these earlier studies in order to take advantage of observations made by Blanazs et al., who reported that (i) the mutual incompatibility between PMPC and PEG is sufficient to produce a biphasic aqueous solution and (ii) double-hydrophilic PEG-PMPC diblock copolymers form nanostructures in concentrated aqueous solution. Thus we utilize a judicious binary mixture of PEG and PMPC precursors to conduct the RAFT aqueous dispersion polymerization of HPMA at 50 °C. The resulting [x PEG113 + (1-x) PMPC28]-PHPMA400 diblock copolymers self-assemble in situ to form various copolymer morphologies depending on the PEG/PMPC molar ratio and the overall copolymer concentration. We target vesicles and exploit enthalpic demixing between the PEG and PMPC stabilizer blocks to drive their segregation across the PHPMA membrane. More specifically, the shorter PMPC block is preferentially expressed at the inner leaflet, while the longer PEG block is preferentially expressed at the outer leaflet. Moreover, using a carboxylic acid-functional RAFT agent to prepare the PMPC precursor ensures that the vesicle lumen contains a relatively high concentration of such acid groups. Such vesicles can be utilized as nanoreactors for the spatially-controlled nucleation of magnetite crystals within the lumen. In principle, they may be useful for anti-cancer therapies based on hypothermia treatment.

Magnetite-loaded biocompatible diblock copolymer vesicles

2019 Fall National Meeting

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