Glyco Functionalized Nanoparticles by PISA

Polymerization-induced self-assembly (PISA) has recently emerged as a straightforward methodology for in situ preparation of nano-objects with tuneable shape and dimension. Despite that it still present some limitations as discussed in Chapter 1.

Through coupling PISA with the highly efficient copper catalysed alkyne-azide cycloaddition (CuAAC) click chemistry, facile strategy for the design of compositionally versatile nanoparticles (NPs) can be realised. 

The combination of PISA and CuAAC in this work readily allows for the preparation and post-functionalization of NPs via incorporation of a reactive propargylic moiety within the hydrophilic shell of the NPs. Initially, a poly(ethylene glycol methyl ether methacrylate)-statistical-poly(propargyl methacrylate) [P(PEGMA)]18-s-P(PgM)5] copolymer was obtained by conventional atom-transfer copolymerization (ATRP). The hydrophilic macroinitiator was then chain extended with 2-hydroxypropyl methacrylate (HPMA) via SET-LRP, yielding self-assembled [P(PEGMA)]18-s-P(PgM)5-b-[PHPMA] NPs, in a process termed aqueous dispersion single electron transfer living radical polymerization induced self-assembly (SET-LR-PISA). After fixing the molecular weight of [P(PEGMA)]18-s-P(PgM)5] to 6.2 kDa, the HPMA DP was varyied, conversion was tracked using 1H NMR spectroscopy, with polymerisation stability of improved through the addition of tetrabutyl ammonium salt during the reaction. Residual copper quantities in the final diblock copolymer were assessed by inductively coupled plasma mass spectroscopy (ICP MS) analysis. After the NPs size and shape were analysed via dynamic light scattering (DLS) and transmission-electron microscopy (TEM), the NP corona could be successfully decorated with various chemical tags through CuAAC. Highly efficient reactivity with fluorescein azide and mannosyl derivatives demonstrates that the system provides a unique platform for the preparation of chemically modular materials though a unique polymerisation method for NP preparation.