Scientists develop “Malteser-like” molecules with potential applications in targeted drug delivery

Posted on: 13 January 2025

Their “Malteser-like” molecules could one day have a suite of applications – from highly sensitive and specific sensors, to next-gen, targeted drug delivery agents.

Virtually all the components of biological systems show an extraordinary and precise ability to self-assemble in the exact way they need to in order to produce the molecules that do the billions of vital things that allow organisms to not only survive, but to thrive, in ever-changing environments.

But despite tremendous scientific advances, researchers are still largely in the dark as to precisely how these processes are governed. The challenge – and tremendous opportunity – for chemists is to decode these processes and then exert control over them to reproducibly programme molecules to do certain things.

We are now closer to that realisation thanks to a landmark piece of work, recently published in the leading international journal of chemistry, Chem (Cell Press). 

The work was performed by a team of scientists led by Prof. Thorfinnur Gunnlaugsson, based in the Trinity Biomedical Sciences Institute (TBSI), in collaboration with Prof. John Boland, based in CRANN. Both groups are part of Trinity College Dublin’s School of Chemistry and the AMBER Research Ireland Centre; while Prof. Robert Pal, Department of Chemistry, Durham University, was also a key collaborator. 

First author, Aramballi Savyasachi, a former PhD student in Trinity’s School of Chemistry, who is based in TBSI, said: “We have been able to make amino-acid-based ‘ligands’ whose self-assembly structures vary – predictably and reproducibly – depending on which amino acid we use. Amino acids are known as the building blocks of life, as they combine to make proteins. Different sequences of amino acids build a huge diversity of different proteins, which have billions of different functions.

“With that in mind, it is perhaps unsurprising that different amino acids produce different self-assembly results – sometimes giving a soft, gel-like material, and other times giving much harder, ‘Malteser molecules’. What did surprise – and delight – us was the discovery that we can largely govern the process and the outcome by selecting specific amino acids. And when we added other molecules, like lanthanide ions, we can tap into luminescence applications.”

Prof. Gunnlaugsson, from the TBSI team, said: “There are so many potential applications of this work and as always, a lot more to learn. But the molecules we have developed already could one day be useful in photonics and optical systems, where highly specific sensors are prized, or in highly targeted drug delivery applications.

“For example, key enzymes appear in greater numbers when the body is fighting an infection and start to break molecules down. The products of this molecular breakdown could stimulate activity in such a way that a drug is released where and when it is needed, which would minimise some of the side effects that come with many, less targeted therapeutics.” 

An additional benefit is that you could potentially monitor activity in the body, in real time, based on luminescence.

Dr Oxana Kotova, Trinity, from the TBSI team, added: “Luminescence is a very useful product of some molecular interactions from a biomedical perspective. In collaboration with Professor Robert Pal at the University of Durham we found that our “Malteser-like” assemblies functionalised with lanthanide ions emit circularly polarised light. This property can allow for visualisation of site-specific interactions within biological media or find an application in optoelectronic devices. 

“I would like to say that this work was only possible thanks to the multidisciplinary collaboration between chemists, biochemists, materials scientists, and physicists lead by Profs. Thorfinnur Gunnlaugsson, John J. Boland, Robert Pal, Matthias E. Möbius and D. Clive Williams.”

Commenting on the significance of the work, Professor Ronan Daly, from the Department of Engineering, University of Cambridge, who was not involved in this study but who is an expert in the field, said

“Engineers and scientists have been pushing the boundaries of manufacturing for a long time, taking materials around us and machining or shaping them into ever smaller and more precise structures. We can do this ‘top-down’ approach so well that it is used in pretty much every manufactured component you see, all the way down to the micro and nanoscale structures in computer chips. Nature, however, never ceases to inspire scientists and engineers, with the incredible ability to create complex molecular structures that somehow click together perfectly at the molecular scale, then those click together at a nano scale and can build up entirely on their own to form things we see and take for granted every day. 

“This self-assembly is an incredibly exciting topic of research where we design materials ‘bottom-up’ with molecules naturally coming together to form what we need. It is of course really complicated and very difficult to design and control, we are just not as good as nature yet!  

“This is a very exciting, highly rigorous piece of work that gives new insights into this molecular-scale control of self-assembly. This helps the whole field move forward by building our understanding and provides a very repeatable and robust way of making these new nanoscale spheres that may one day be used, for example, in the future of drug delivery, flowing around the body and releasing a target drug or gene therapy to the right location."

This work was funded in part by Taighde Éireann – Research Ireland, formerly Science Foundation Ireland and a Royal Society University Research Fellowship.  

The article can be read on the publisher's website. 

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