2024 Kavli
Prize in
Nanoscience

Citation from the Committee

One of the most virtuous goals of science is that of preserving health and saving lives. The 2024 Kavli Prize in Nanoscience honors three pioneers whose breakthroughs have combined nanostructured synthetic materials with biologically active molecules. They have pioneered their use in therapeutics, vaccines, bioimaging and diagnostics, contributing foundationally to the field of nanomedicine. In addition, the three laureates have contributed to the societal impact of their research by founding companies to translate their fundamental science into biomedical applications.

Robert S. Langer had the breakthrough idea that a material could be “nano-engineered” for the controlled release of therapeutic biomolecules.While Langer’s ideas were initially received with skepticism, he showed that polymers could be synthesized to permit the regular flow of drug molecules through channels in the material.This idea has had profound impact on the development of controlled drug delivery systems. Langer’s work has had immense clinical impact for the treatment of diseases such as aggressive brain cancer (glioblastoma), prostate cancer and schizophrenia. Langer also showed, as far back as 1979, that tiny particles (in this case containing protein antigens) could be used for vaccination.

Armand Paul Alivisatos pioneered the use of semiconductor nanocrystals for biological imaging by tailoring them through surface functionalization. Semiconductor nanocrystals, or “quantum dots”, are nanoparticles that possess bright, size-dependent light-emitting properties. Alivisatos showed that these nanoscale “beacons” can be used as multicolor fluorescent probes in biological imaging. Semiconductor nanocrystals are widely used today in applications such as live cell tracking, labelling and in vivo imaging.

Chad A. Mirkin introduced the concept of the spherical nucleic acid (SNA) consisting of a nanoparticle core coated with a dense layer of oriented synthetic DNA or RNA. This nanoparticle-biomolecular complex gives rise to a very high binding specificity combined with a nanoparticle reporter. With SNAs, Mirkin has been able to show ultrasensitive and selective detection of proteins, DNA and RNA. This has led to a fast, automated point-of-care medical diagnostic system.

Prize share: Robert S. Langer ½, Armand Paul Alivisatos ¼, Chad A. Mirkin ¼

When nanoscience met medicine

The ability to engineer materials at the nanoscale can lead to the use of nanoparticles in a wide range of applications. The 2024 Kavli Prize in Nanoscience highlights the fundamental contribution that nanoscience and nanotechnology have given to biomedical research.

By Fabio Pulizzi, science writer

In making their award, the Kavli Prize in Nanoscience Committee has selected three scientists for their pioneering work on synthetic nanoscale materials with biological functions for biomedical applications, leading to improved drug delivery, bioimaging and biodiagnostics.

Almost sixty years ago, 20th Century Fox brought to the movie theatres one of the most memorable science fiction movies of all time. “Fantastic Voyage”, released in 1966, shows a submarine and its crew being shrunk so much that they could enter the blood stream of a scientist and repair some brain damage. Miniaturizing a team of surgeons will remain an impossible dream. However, the work by scientists like Robert S. Langer, Armand Paul Alivisatos and Chad A. Mirkin has shown us that it is possible to engineer nanoparticles such that they are closer to being able to do what a miniature surgeon would.

In the early 1970s, when Robert S. Langer finished his studies, he decided to take an unusual path for a chemical engineering graduate. Instead of seeking a job in a large chemical company, he joined the lab of biologist and tumour expert Judah Folkman as a postdoctoral researcher. He wanted to use his expertise in manipulating chemicals and materials to improve the controlled release of drugs. Folkman himself had demonstrated in 1964 that it was possible to encapsulate small-molecule drugs into silicon rubber capsules. Once inserted in the aqueous environment, similar to that of a living organism, the small molecules diffused through the silicon rubber membranes [1]. Although a fundamental result, Folkman’s method did not work for large molecules, for example proteins. Langer’s approach was to disperse the molecules in a polymer matrix nanoparticle, and once in aqueous solution the molecules would then be released by moving through the channels in the matrix. He tried a wide range of synthesis conditions and polymeric structures, and after numerous attempts he was able to demonstrate the controlled release of proteins, for over 100 days, from a polymer matrix [2]. Furthermore, the polymer used, namely ethylene-vinyl acetate copolymer, was tested for potential inflammatory effects, and was found to be much safer than silicon rubber or other candidate polymers.

After the initial results, Langer kept working on the development of materials to improve controlled release. In 1987, he published a paper demonstrating a class of polymers that would slowly erode when in contact with a cellular environment. That way, the drugs dispersed in the polymer matrix would be released according to the polymer erosion, rather than just having to flow out of channels in the matrixes [3] (Figure 1).This approach would even be used, in a collaboration with Henry Brem of Johns Hopkins University, to deliver antigens to brain cancer cells, showing in a practical way its potential for drug delivery [4]. 

Langer and his collaborators have achieved several milestones in drug delivery since his first results, and many of them have been translated through the launch of startup companies. Perhaps most notable was his first work on the delivery of vaccines [5] that would eventually lead to the company Moderna and the development of mRNA vaccines for COVID 19.

While Langer worked primarily on drug delivery, Armand Paul Alivisatos approached biomedical research by focusing on imaging. His appointment as an assistant professor at the University of California, Berkeley in 1988 came only a few years after Louis Brus’s pioneering work on the colloidal synthesis of semiconductor nanocrystals, also known as quantum dots, which earned him both the Kavli Prize in Nanoscience in 2008 and the Nobel Prize in Chemistry in 2023. The appeal of quantum dots was extraordinary. Once illuminated by a laser beam, they emit light at wavelengths determined quite precisely from their size in the nanometre range. They could potentially be used in optoelectronics devices like LEDs, solar cells or TV displays, as well as fluorophores in biomedical imaging. Because the light emission of quantum dots of different sizes can be triggered by the same laser, one could design imaging with different colours. This had so far not been possible with organic dye molecules used in bioimaging. The difficulty, however, was to produce large amounts of quantum dots with a specific size in reliable way. Using his skills in chemical synthesis, Alivisatos demonstrated how the various processes of the synthesis of quantum dots have an impact on the size and hence on the optical emission, publishing the results in a milestone paper in 1998 [6]. In the same year, Alivisatos and his team demonstrated the use of semiconductor nanocrystals as fluorescence labels in mouse 3T3 fibroblasts. An essential step in achieving imaging in tissue was to add a silica layer to the quantum dot so that the nanoparticles would be biocompatible and stable in an aqueous solution. Following this route, the team produced a two-colour image with a single illumination source [7] (Figure 2). Since 1998 Alivisatos’s work has led to the synthesis of quantum dots with a variety of shapes and sizes, and his results have been brought to the market via several startups, including the Quantum Dot Corporation, which produces quantum dots for imaging.

Maybe as a sign of fate, back-to-back with the paper in which Alivisatos’s group reported a structure composed of two quantum dots held together by a DNA strand [8], Chad A. Mirkin and his co-workers published a structure that would become known as a spherical nucleic acid (or SNA) [9]. The structure shown by Mirkin and colleagues consisted of a gold nanoparticle, only 13 nm in diameter, encapsulated in a shell of radially distributed single DNA strands. In later work Mirkin and team were able to create SNAs having different nanoparticle cores (Figure 3).

The beauty of an SNA is that it can be used as a building block for larger structures in which the single SNAs are glued together by matching DNA strands, with the physical properties of the resulting structure changing according to the length of the DNA connectors. For example, Mirkin and co-workers were able to demonstrate that the DNA strands attached to gold nanoparticles could be designed to match the specific DNA strands that were to be detected in extracellular conditions [10]. When the target DNA sticks to the SNA, the latter changes its optical emission wavelength. That way, the SNA can be used for the identification of DNA associated with certain conditions. The results of this experiment led to the development of the VERIGENE® biodiagnostic system commercialized by the startup Nanosphere Inc. The work described in the 1996 paper gave birth to a new field in chemistry and nanoscience, in which Mirkin has played a primary role.

“Langer, Alivisatos and Mirkin are science pioneers. Building from fundamental research and scientific curiosity they have become inventors and major founders of the nanomedicine field”, says Bodil Holst, Chair of the Nanoscience Committee.

References

1. Folkman, J. & Long, D. M. J. Surg. Res. 4, 139–142 (1964).
2. Langer, R. & Folman, J. Nature 263, 797–800 (1976).
3. Domb, A. J. & Langer, R. J. Polym. Sci., Part A: Polym. Chem.25, 3373–3386 (1987).
4. Brem, H and Langer, R., Science and medicine 3, 52-61(1996)
5. Pres, I. & Langer R. S. J. Immunol. Methods28, 193–197 (1979).
6. Peng, X., Wickham, J. & Alivisatos, A. P. J. Am. Chem. Soc. 120, 5343–5344 (1998).
7. Bruchez, M. Jr, Morrone, M., Gin, P., Weiss, S. & Alivisatos, A. P. Science 281, 2013–2016 (1998).
8. Alivisatos, A. P. et al. Nature 382, 609–611 (1996).
9. Mirkin, C. A., Letsinger, R. L., Mucic, R. C. & Storhoff, J. J. Nature 382, 607–609 (1996).
10. Nam, J. M., Thaxton, C. S. & Mirkin, C. A. Science, 301, 1884–1886 (2003).