PhD Discussions: José Muñoz-López

Design and characterization of bifunctional hydrophilic Janus micelles

José Muñoz-López, Molecular Bionics Group

Janus micelles are featured by their biphasic geometry of heterogeneous composition and distinctive properties in the core and corona. Such anisotropic design has attracted much attention from the scientific community due to the versatility of chemistries employed for generating Janus’ morphologies and their potential applications. In this work, we present a novel ABC amphiphilic triblock copolymer system with the ability to form Janus micelles. The micelles are generated by solution-mediated self-assembly of the A and C hydrophilic, and B hydrophobic blocks. Subsequently, the hydrophilic blocks in the proposed triblock system will be functionalized with different and specific bioactive ligands to enable the constitution of multifunctional supramolecular scaffolds. The final aim of the project herein presented is to develop nanodrugs with well-defined dissimilar phenotypical domains, in the same fashion as the asymmetric functionalisation of antibodies that already exist in nature, to perform alike. To this end, poly(ethylene glycol)-polylactide-poly(N-vinylpyrrolidone) PEG-PLA-PVP triblock copolymer was synthesised in two steps: first, poly(ethylene glycol)-polylactide-2-bromo-2-methylpropanoate (PEG-PLA-Br) diblock macroinitiator was synthesized by the ring-opening polymerization of DL-lactide with commercial poly(ethylene glycol) and quenched with 2-bromo-isobutiryl-bromide. After that triblock copolymer was synthesized by the atom transfer radical polymerization (ATRP) of N-vinylpyrrolidone monomer (NVP) initiated by the PEG-PLA-Br diblock produced in the former synthetic step. The characterization of the produced diblock and triblock copolymers were carried out by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). Such techniques enabled us to verify the controlled radical polymerization of NVP and the complete conversion of PEG-PLA-Br diblock to the proposed PEG-PLA-PVP triblock. The morphologies adopted by PEG-PLA-Br and PEG-PLA-PVP in solution were investigated by transmission electron microscopy (TEM), confirming the formation of micelles for both block copolymers. TEM images showed differences in the negative stained micelles generated in the diblock and triblock copolymers systems. Such differences indicate the asymmetric distribution of both hydrophilic blocks, PEG and PVP, in the self-assembling of the PEG-PLA-PVP triblock system. Further structure characterizations will include atomic force microscopy (AFM), cryo-TEM, electron energy loss spectroscopy (EELS), and ultimately the functionalization of both coronas with different targeting ligands.

This PhD Discussion session will be held at Tower I, 11th floor Baobab room, at 10:00am.

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