Molecular Switch Nanoparticles for Redox-Triggered Drug Delivery

About the Project

Oxidative stress is a defining feature of several chronic diseases, including cancer, diabetic complications, and neurodegenerative disorders. In these conditions, affected tissues exhibit dramatically elevated levels of reactive oxygen species (ROS) and glutathione, often 4 to 20 times higher than in healthy tissue. This biochemical gradient presents a unique opportunity for designing stimulus-responsive drug delivery systems that selectively release therapeutic agents at disease sites, without the need for complex targeting ligands. Alpha-lipoic acid (ALA), a naturally occurring and clinically safe compound, offers a promising solution. Its 1,2-dithiolane ring structure functions as a molecular switch, remaining stable under normal physiological conditions but opens under reducing conditions, triggering drug release.

This PhD project aims to develop an oxidative stress-responsive nanoparticle platform for precision drug delivery. The successful candidate will design and synthesise ALA-drug conjugates using bioconjugation chemistry and encapsulate them into nanostructured lipid carriers (NLCs). These will be formulated using high-pressure homogenisation techniques and characterised by dynamic light scattering, advanced microscopy techniques, and spectroscopy. Initial studies will use fluorescent model compounds to investigate release mechanisms, followed by translation to therapeutic agents. Drug release will be evaluated through in vitro studies across physiologically relevant oxidative stress gradients, from normal tissue to pathological conditions. This project is particularly well-suited for candidates with an interest in chemical biology and drug delivery, with scope to tailor the disease focus based on student interests and collaborative opportunities.

Briefly describe the training that will be provided through the research project

Training will be provided in bioconjugate chemistry, nanoparticle formulation, analytical techniques (HPLC, microscopy, spectroscopy), drug release modelling, and in vitro cellular studies. The student will also develop core research skills in scientific writing, literature review, time management, and presentation delivery.

Briefly outline the expected impact activities

The PhD student will be encouraged to disseminate research findings through publications, public talks, and participation in QUB showcase events.