The aim is to activate medicines precisely where and when needed, minimising side effects and maximising effectiveness.
Dr. Hartmann's work addresses a key limitation in current therapies: drug targeting. He focuses on macrocycles, a class of ring-shaped drugs with significant therapeutic potential.
Many macrocycles are already in use, but often struggle to reach their intended site effectively, or they cause unwanted side effects by affecting healthy tissues - remote control over their activity within the body is currently absent.
The project will research the potential of creating tiny "molecular trains" called rotaxanes. These act as microscopic delivery vehicles. The macrocycle drug threads onto a molecular axle and is held by stoppers - think of beads on a bracelet. In this packaged state, the drug remains inactive.
The system's control lies in the axle, which incorporates a switch responsive to external signals. When the specific signal is present (light, pH change, or disease-specific enzymes), the stoppers are removed or the axle changes configuration. This allows the drug to slip off the axle and become active in the precise location that it needs to.
Macrocycles are an exciting class of molecules and developing them into ‘molecular capsules’ that can respond to their environment will open up new avenues for their application in biology and medicine.
Dr Denis Hartmann
This smart delivery system offers several benefits for future medicines including drugs being delivered to specific cells or tissues, reducing the side effects, improved effectiveness of drugs and the ability to interchange drugs, axles and triggers for more customisable therapies.
This pioneering work from the University of Sheffield, supported by the Leverhulme Trust, is crucial for developing a new generation of safer, more effective precision medicines.
"We are very excited that Denis will soon join us in Sheffield, bringing expertise in the design and applications of macrocycles in drug delivery and as tools in Chemical Biology." Dr David Williams