Mitochondria are the power plants of our cells. When they malfunction, serious diseases can arise, including cancer, Parkinson's disease and rare genetic disorders. Although delivering medicines directly to mitochondria has enormous therapeutic potential, existing approaches rely on complex chemistry that is difficult to scale up for manufacturing. As a result, no mitochondria-targeted therapy has yet reached patients.
During an earlier ERC Consolidator Grant project, Wilson and her team discovered a new way of attaching targeting molecules to drug delivery carriers, enabling medicines to reach their intended destination within the cell more effectively. The newly awarded NWO Demonstrator Grant will help translate this discovery into a practical technology.
Serendipity
The research group was originally working on nanoparticles designed to move like tiny locomotives. To enable this movement, the researchers wanted to chemically attach molecules to the surface of the particles. ‘My postdoctoral researcher Shaohua Zhang discovered that the molecules were attaching themselves to the particles spontaneously. We did not expect that,’ says Wilson.
Together with modelling experts, the team investigated what was happening. They found that the protective coating already present on many drug delivery carriers can be activated under specific conditions. This creates what Wilson describes as a molecular "Velcro grip" that captures targeting molecules. As a result, existing drug carriers can be functionalised much more easily, without complicated chemical reactions.
The findings were published in Nature Chemistry in 2023, and the researchers have since filed a patent application.
The power of simplicity
The new approach differs significantly from conventional methods. Traditionally, targeting molecules are chemically attached to a drug carrier using complex chemical reactions. This process is time-consuming, often requires harsh chemicals, and can even damage the carrier itself.
With the new technology, this is no longer necessary. By simply mixing the components in a biologically relevant solution, such as water-based buffer systems, the targeting molecules rapidly anchor themselves to the carrier. No organic solvents or harsh chemicals are required.
‘This offers major advantages for the pharmaceutical industry," says Wilson. "Companies can keep their existing formulations and simply add a recognition molecule, without having to redevelop and revalidate the entire product.’ In the longer term, more precise drug delivery could help reduce side effects for patients while also decreasing waste in manufacturing processes.
A Mix-and-Match Platform for multiple applications
For the Demonstrator Grant, Wilson deliberately chose mitochondria as the first application, not because they are the easiest target, but because they are among the most challenging. ‘We also looked at where the biggest challenges and opportunities lie for the pharmaceutical industry,’ she explains.
However, the underlying principle is not limited to mitochondria. By changing the targeting molecule, the same "mix-and-match" platform could be used to direct drug carriers to different cell types or tissues, including combining treatment with diagnosis. In a parallel project funded by an ERC Proof of Concept grant, Wilson's team is using the same anchoring trick for targeted imaging: attaching a homing molecule and an MRI contrast agent onto the same carrier, so that a scan lights up cancer cells directly, rather than relying on today's contrast agents, which can't tell cancer from healthy tissue. 'It's the same Velcro principle,' says Wilson. 'One platform, and depending on what you attach to it, it can deliver a treatment or light up a diagnosis a step toward what's called theranostics, treating and detecting disease at once.'
Goal
The Demonstrator project will run for 18 months. ‘During this period, we want to demonstrate, in collaboration with pharmaceutical companies, that the technology can be applied to their existing drug formulations. We want to show that our technology offers advantages over current methods and may even help reduce production costs,’ says Wilson. If successful, the discovery could represent an important step towards more precise drug delivery and new treatment options for diseases in which mitochondria play a role.
Wilson adds: ‘The ultimate goal is to help patients, for example by reducing side effects. If we can demonstrate that a medicine specifically reaches the mitochondria, this could open up new possibilities for treating a wide range of diseases in the future.’
