In a new review article, Prof. Angela Casini and co-authors explore the advantages of supramolecular platforms for cancer therapy and diagnosis. They focus on the radiopharmaceutical and potential clinical applications of self-assembling coordination complexes, metallacages, rotaxanes and supramolecular aggregates that form in situ. In an interview, we asked the team – Dr. Guillermo Moreno-Alcántar (GMA), Marike Drexler (MD), and Prof. Angela Casini (AC) – for their insights onto new supramolecular theranostics.
Why is a new review article about this field needed right now?
AC: There are several high-quality review articles on radiopharmaceuticals, however, not in the field of supramolecular-based strategies. We had to be very concise, but also target different audiences [which is] why we discussed certain concepts in a tutorial-like fashion, while trying to maintain a specialist language. That was very challenging for us!
Dr. Guillermo Moreno-Alcántar highlights the gap in supramolecular chemistry, where much of the focus is on fundamental research, structural studies, and biomimetics, but there is a lack of emphasis on practical applications. He mentions his disciplinary transition from classical supramolecular chemistry to medicinal applications, noting that while there is growing interest in life-like systems, there is not enough effort to push these discoveries toward real-world applications.
GMA: The people we cite, including Angela, of course, are fostering efforts to take existing knowledge in supramolecular chemistry, a field that is currently thriving, but there is limited focus on applying it for medical use.
Writing review articles in any field simultaneously documents current information while offering co-authors a unique opportunity to develop their research expertise. We asked Angela to summarize what is known now and where there is room for further development.
In the course of creating the review, was there something special about what you found?
AC: There are three approaches in this field: one is based on self-assembled metallacages, the other on rotaxanes, so purely organic interlocked molecules, and then finally, there is the in situ self-assembly of supramolecular aggregates. I was less familiar with the latter, and I enjoyed taking a deeper look into it.
From your perspective, what are the particular challenges designing supramolecular theranostics?
AC: For radiopharmaceutical applications, the principles of self-assembly need to be adapted and reconsidered due to the vastly different experimental conditions and concentration ranges (from millimolar to nanomolar) compared to classical supramolecular chemistry. As a consequence, the radiopharmaceutical chemistry community operates differently, typically not using NMR spectroscopy for final product characterization.
What are your personal takeaways from writing this kind of article, Marike?
MD: This review offered me a great opportunity to gain an overview of the field, which is especially helpful for structuring the introduction of a doctoral thesis and will for sure be very important for my PhD defense. Also, doing this work together with a team of experts prepared me to write the first research articles on my own.
Will this review article have an impact on current or future research projects?
AC: What I am interested in as PI are mechanisms. It doesn’t really matter if they are inorganic, organic, or supramolecular. I moved from small molecules to supramolecules in the last 8 years. The application to pharmaceutical radiochemistry followed my appointment as ad interim Chair of Pharmaceutical Radiochemistry. This is the beauty of being in one of the big Universities – there are a lot of opportunities you can capitalize upon.
So, to answer your question, this review in Nature Chemistry Reviews is meant to be a reference for interested scientific communities that I would like to present at conferences to draw attention to the new developments. The manuscript is also a milestone in our newly funded European Pathfinder Project (SMARTdrugs) on the assembly of the next generation of radiopharmaceuticals. SMARTdrugs is one of the flagship projects of the TUM Center for Smart Drug Design, tackling highly interdisciplinary biomedical research.
The review contributes to existing knowledge on the topic as well as to the education of future experts, like PhD student Marike Drexler, whose contribution as co-author has broadened her knowledge in the field.
Does it help to have a PhD student on board, Angela?
AC: Of course! Marike knows much more in this field than me right now. For me, it is very important to get the input of our students, especially when it comes to making it more accessible to a broader audience.
As a doctoral student, Marike, would you recommend writing a review article to other students?
MD: Although it takes time away from working in the laboratory, gaining an overview of the field is valuable; some PIs even require students to write a review at the start of their doctorate to ensure they have a solid theoretical background. All in all, I would recommend writing such an article.
TUM is not only excellent in science, but also in teaching. Angela, you received the Golden Chalk Award from our students for excellent teaching in Pharmaceutical Radiochemistry classes. How will this review article affect teaching in your classes?
AC: I think Marike can answer that question as she has already given the first lecture on this topic in one of the radiochemistry courses (Special Aspects in Radiochemistry) of last year.
MD: I gave a lecture on radiolabeled supramolecules this summer for the first time. We have several elective modules where modern aspects of radiochemistry are addressed.
AC: The topics we choose for the lectures are updated each year, so we make sure that every new aspect of this research field is addressed. We also hope to attract internship students with these highly interdisciplinary lectures that display the “state-of-the-art” research.
Dear Marike, Angela, and Guillermo, thank you for taking the time for such a wonderful interview!
Publication:
Nature Reviews Chemistry: “Assembling a new generation of radiopharmaceuticals with supramolecular theranostics”, DOI: https://doi.org/10.1038/s41570-024-00657-4 (Published: 28th October 2024)
Further Information and Links:
- Prof. Angela Casini, Chair of Medicinal and Bioinorganic Chemistry
- Center for Smart Drug Design
- SMARTdrugs: The radical long-term vision of SMARTdrugs is to harness the untapped potential of supramolecular chemistry to create a new class of therapies – radiotheranostics – which combine both diagnostic and therapeutic radionuclides in one compound. By using the self-assembly of host-guest supramolecular coordination complexes and molecularly interlocked molecules as scaffolds for creating supramolecular radiotheranostic drugs, new methods for radiotheranostic synthesis that break away from conventional medicinal chemistry concept will be introduced.
- News-article for SMARTdrugs
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