Interview with Lorenzo Albertazzi

Trespassing the limits of lights - Lorenzo Albertazzi

Trespassing the limits of lights

Lorenzo Albertazzi is associate professor in the research group of Molecular Biosensing for Medical Diagnostics, at the Biomedical Engineering department at TU/e. Albertazzi is also junior group leader at the Institute of Bioengineering of Catalonia (IBEC) in Barcelona, where he leads the Nanoscopy for Nanomedicine group. In his research, Albertazzi aims to achieve a molecular understanding of synthetic materials in the biological environment, using both optical microscopy and nanoscopy. The ultimate goal of his research is to design nanomaterials for the next generation of targeted, super-efficient cancer treatments.

Over the last decades, the engineering of materials to the nanometer scale has opened up for novel and promising medical therapies, such as the design of nanoparticle-based drugs for cancer treatments. As in the case of the research performed by Lorenzo Albertazzi within the Biomedical Engineering Department and ICMS at TU/e. Albertazzi: “Within the nanomedicine field, we are trying to develop nanoparticles for targeted drug delivery, with prostate and breast cancer as main applications.”



“The field of nanomedicine is as big as it is crowded”, says Albertazzi, “yet, we try to tackle it via our own, original angle: the use of advanced microscopy. This is also our main technical expertise, with super resolution microscopy being one of our favorite techniques.”



Albertazzi: “Optical microscopy is one of the most used type of imaging, since hundreds of years. However, the resolution of optical microscopy is limited by the intrinsic nature of light, which makes it impossible to visualize objects smaller than 200- 300 nm.” Held back for a long time by this assumption, optical microscopy found a new twist in the last decade of the 20th century, when the 2014 Nobel Laureates in Chemistry circumvented this limitation, bringing optical microscopy into the nanoscale. Albertazzi: “Super resolution microscopy is an optical technique which by-passes the limits of conventional optical microscopy. The name itself is very explicative. It is an optical technique with better resolution, meaning that you can resolve much smaller objects, even at the nanometer scale.”



Albertazzi: “We make objects that are small and very challenging to characterize.” For Albertazzi and his team, advanced optical microscopy is the enabling technology to solve this challenge. “Besides being extremely helpful for the characterization of our nanoparticles in the laboratory”, explains Albertazzi, “optical microscopy can be used in cells, human tissues and organs.” Highly complex cellular environments where details matter. Albertazzi: “With super resolution microscopy, we can target subcellular organelles and even single proteins. For example, in the case of nanoparticles and their interactions with cells, we can see to which and how many cellular receptors the nanoparticles bind to.”



Albertazzi: “Super resolution microscopy is a quite recent technique. The first papers were published approximately 10 years ago. When we bought our first microscope for STORM - Stochastic Optical Reconstruction Microscopy - there were only few other comparable microscopes in Europe. Also, back then, super resolution microscopy was mainly intended for biologists and no one had ever performed measurements on synthetic objects. Thus, the first big step for us has been to measure a man-made object, which was not obvious because of the substantial differences in sample preparation and imaging procedures we had to deal with.” A huge effort for Albertazzi and, amongst others, Bert Meijer and Remco van der Hofstad, which was rewarded with a publication in Science in 2014.



Worldwide, research on nanomedicine is now driven by innovators across disciplines such as engineering, biology, medicine, and chemistry. Albertazzi: “Our work implies a multidisciplinary approach, which requires a joined effort from all the different scientific communities involved. Very often biophysicists don’t know about chemistry, and chemists don’t know about optical microscopy. Yet, to answer specific questions, you need to master biology, chemistry and microscopy. The magic happens when you combine these fields. In this sense, ICMS was the perfect place to do so.”



Albertazzi: “Nanomedicine for cancer treatment is out since many years, to the point that it can almost be considered as an old research field. The amount of publications within this field is enormous. Yet, if you look at what’s brought in the clinic, there is almost nothing out there. After the first drug was approved for clinical use, in 1997, only a few drugs have been approved, which are all very similar to each other and not very sophisticated.” So, why the big promise of nanomedicine has not delivered yet? Possibly due to “knowledge gaps” - as Albertazzi defines them - between the behavior of drugeluting nanoparticles in vitro (in the laboratory) and their interactions with cells in vivo (in the human body). Albertazzi: “Nowadays we are capable of characterizing nanoparticles in the laboratory in a pretty adequate way. However, once these nanoparticles are injected in the human body, their behavior and their side-effects in such a black box remain very difficult to understand.” And that is where the challenge for Albertazzi and colleagues starts: “We want to understand and characterize the behavior of nanoparticles from the moment of their injection in the patient to the very end-phase. Rather than going for lucky shots, we want to decompose the problem and answer fundamental questions first.” The answers to those questions provide Albertazzi and his colleagues the key information that will allow the design of the next generation of nanoparticles: precise, effective and safe therapeutic tools for clinical use.