Nanomedicines Prepared using Polymerization Induced Self-Assembly (PISA)

Background: Recent advances in polymer particle design have largely relied on developments in controlled/living or reversible deactivation radical polymerization (RDRP). The most widely used and versatile RDRP is Reversible Addition Fragmentation Chain Transfer (RAFT). Recently, our group used RAFT-mediated solution polymerizations to prepare the first high aspect ratio lactate and glucose-responsive nanoparticles [1]. Upon dialysis amphiphilic block copolymers, self-assemble into core-shell nanoparticles with the boronic acid (BA)-functionality at the core, enabling stimuli-response. Lactate detection is useful for treatments or monitoring of pathological conditions such as exercise, injury, and cancer, while glucose detection allows the development of drug-releasing platforms for the treatment of diabetes. BA binding to lactate and glucose converts solvated hydrophobic polymer into core-shell nanoparticle spheres and worms [2]. RAFT implemented as a dispersion polymerization, allows the preparation of high concentrations of well-defined higher order BA-containing nanoparticles, including vesicles in a single-step process, called polymerization induced self-assembly (PISA) [3]. Drug delivery with polymer nanoparticles offers therapeutic advantages, such as a large surface area for improved biocompatibility, enhanced cell permeability, and activation of therapy in response to specific physiological condition(s). As well as polymer synthesis, the Aldabbagh group has a track record in the discovery of anti-cancer heterocyclic quinone scaffolds [4-6]. 

The Project: The aim is to produce nanomedicines by incorporating heterocyclic anti-cancer agents into stimuli-responsive nanoparticles using PISA. This will be achieved by encapsulating the anti-cancer agent using the benign conditions of a visible-light mediated photo-PISA or by synthesizing new bioactive heterocycles that can also act as initiators for photo-PISA. Visible light can activate quinone methide (QM) formation, which is an alternative to Nature’s enzymatic reductive activation (e.g., of the clinically used anti-cancer agent, mitomycin C) [7]. Such light sensitive compounds will be used to develop new PISA technology for the synthesis of the proposed nanomedicines. 

Training provided: Synthetic organic and polymer chemistry and associated analytical chemistry. There is an established collaboration with the group of Prof. Per B. Zetterlund (UNSW, Australia) on the use of state-of-the-art nanoparticle characterization techniques. Drug-delivery studies will be carried out through collaborations with colleagues at the Department of Pharmacy, Kingston University.