Three microscopes in one: NanoLights reveals hidden differences between nanoparticles
黑料福利网 researchers Lorenzo Albertazzi (Biomedical Engineering) and Peter Zijlstra (Applied Physics and Science Education) have received a 鈧�950,000 NWO Open Technology Programme grant to develop NanoLights. With additional contributions from industry partners, the total project funding amounts to 鈧�1.2 million. Over the course of four years, the researchers will develop a new optical instrument that can investigate nanoparticles using multiple complementary techniques simultaneously.
Nanoparticles are playing an increasingly important role in medicine. Synthetic nanoparticles, such as lipid nanoparticles, are used to deliver mRNA and other therapeutics. At the same time, naturally occurring nanoparticles such as extracellular vesicles (EVs), released by cells, are showing great promise for therapeutic and diagnostic applications.
To understand why some nanoparticles perform better than others, researchers need to look beyond population averages and study particles at the individual level. Nanoparticles can vary considerably within the same batch, and these differences may have a major impact on their biological function.
From averages to individual particles
鈥淚t鈥檚 like looking at the average height of a group of people versus looking at each individual,鈥� explains Lorenzo Albertazzi. 鈥淎n average height of 1.70 meters does not mean that everyone will fit through a 1.71-meter doorway.鈥�
Similarly, measurements of large nanoparticle populations can obscure important differences between particles. A sample may consist of highly uniform particles, or it may contain substantial variation. In some cases, only a small fraction of the particles may be responsible for the desired therapeutic effect.
NanoLights aims to make these hidden differences visible.
Three microscopes in one
At the heart of NanoLights is the integration of three advanced optical techniques into a single instrument: interferometric scattering microscopy (iSCAT), super-resolution microscopy, and fluorescence spectroscopy.
Each technique provides information about a different aspect of a nanoparticle:
- iSCAT determines properties such as size, shape, and aggregation state;
- super-resolution microscopy localizes and counts molecules on the particle surface, including functional molecules and ligands;
- fluorescence spectroscopy reveals physicochemical properties such as membrane polarity.
The innovation lies not only in combining these three methods, but also in applying them to the same nanoparticle and correlating the results.
This enables researchers to directly link multiple characteristics of the same particle and build a much more complete picture of its properties.
鈥淔rom a technical perspective, I鈥檓 excited about having a device that allows you to look at individual particles from 鈥�360 degrees,鈥欌�� says Albertazzi. 鈥淏ut scientifically, I鈥檓 particularly curious about the role of particle-to-particle heterogeneity. Do all particles behave the same, or are there a few 鈥榦verachievers鈥� among them?鈥�
A collaboration between BmE and APSE
Bringing NanoLights to life requires expertise from multiple disciplines, making the collaboration between the research groups of Albertazzi and Zijlstra central to the project.
Both researchers specialize in microscopy, but from complementary perspectives. Albertazzi contributes expertise in molecular and biomedical applications of nanoparticles as well as super-resolution microscopy.
Peter Zijlstra brings expertise in optics, single-particle scattering microscopy, and the development of custom imaging platforms.
By combining these strengths, the team can create an instrument in which different optical techniques work seamlessly together, providing complementary information about the same particle.
From nanoparticles to better therapies
The researchers will use NanoLights to study both synthetic and naturally occurring nanoparticles. Alongside lipid nanoparticles used for drug delivery, they will investigate extracellular vesicles.
For this part of the project, they are collaborating with the research hospital VHIR in Barcelona. Together, they will investigate how extracellular vesicles are produced in the body and how these naturally occurring EVs differ from vesicles produced outside the body.
This question is particularly relevant because extracellular vesicles could potentially serve as drug carriers or even therapeutics themselves. An important challenge remains: are we producing the right vesicles in the laboratory?
By characterizing individual vesicles in much greater detail, the researchers hope to identify which properties are linked to biological function.
鈥淭he key question is whether all nanoparticles behave the same, or whether a few 鈥榦verachievers鈥� drive the biological effect.鈥�
Lorenzo Albertazzi
In the longer term, NanoLights could contribute to the development of more effective nanoparticles, a deeper understanding of how they work, and potentially new approaches to quality control in the production of nanomedical materials.
Toward predictive nanomedicine
The project also has an ambitious long-term goal. Albertazzi wants to investigate whether the wealth of information generated by NanoLights can eventually be used to develop predictive models that identify which particles are best suited for a particular application.
鈥淭hat may be the most exciting application for me: finding out whether we can eventually feed this data into models that can predict in advance which particle will work best for a particular application.鈥�
With NanoLights, the researchers aim not just to collect more data, but to transform how nanoparticles are studied, moving beyond population averages to uncover the properties that determine why some particles succeed where others do not.
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