Mechanistic insights into polymerization-induced self-assembly using maleimide-based fluorophores

Polymerization-induced self-assembly (PISA) is a versatile and readily accessible method to produce nanoparticles of various morphologies in situ as polymerization progresses. PISA exploits the chain extension of a solvophilic macro-chain-transfer agent with monomers that are miscible in the continuous phase but form a solvophobic, immiscible polymer, driving self-assembly. However, the ability to monitor in situ the onset of self-assembly and evolution of morphology during the PISA process remains a significant challenge which critically limits our understanding of the mechanisms of particle formation. We demonstrate that an aminochloromaleimide (ACM) fluorophore can act as a powerful probe to study PISA over time, using fluorescence and fluorescence lifetime as outputs. The ACM probe exhibits diagnostic increases in fluorescence lifetime first with onset of self-assembly, then with evolution of particle morphology in the order of spheres > vesicles > worms. Excitingly, monitoring the change in fluorescence lifetime in situ during PISA yielded insights into the mechanism of particle formation when targeting higher order morphologies. Overall, we envision this to become a powerful tool for the analysis of nanoparticle states within complex environments, inspiring further investigations into the study of PISA using this simple and accessible method.

Short Bio

Dr Amanda K. Pearce joined the Department of Chemistry as a Lecturer in September 2022. Her research is highly interdisciplinary, focusing on the synthesis and application of fluorescent polymer nanoparticles in a range of healthcare applications. She also acts as an advocate for science engagement with underrepresented groups in the community. Amanda completed her Honour’s degree in Chemistry at the University of Queensland, where she stayed to obtain her PhD in 2015, under the supervision of Assoc. Prof. Kristofer Thurecht and Prof. Andrew Whittaker, focusing on the synthesis of targeted, drug-loaded hyperbranched polymers via RAFT polymerisation for in vivo prostate cancer applications. She then moved to the University of Nottingham, UK in 2016 as a Research Fellow working with Prof. Cameron Alexander in an EPSRC Biomaterials Discovery Programme Grant to further her research on the design, synthesis, and characterisation of novel synthetic polymers for cancer drug delivery. In 2019, Amanda was promoted to Group Leader with Prof. Rachel O’Reilly at the University of Birmingham, where she was the lead researcher of the polymers and self-assembly subgroup, where she worked on projects using fluorescence lifetime as a tool to monitor particle self-assembly and biological behaviours.