Luis Manuel Liz Marzán, chemist: "We listen to what cells say to each other"

The chemist Luis Manuel Liz Marzán, born in Vigo 57 years ago, spies on the cells.

to them

with nanostars (nanomaterials created with gold and silver, mainly, smaller than 100 nanometers or a billionth of a meter) to learn their intentions and strategies.

Its objective is to investigate how to intervene, with the same nanomaterials, in the event that the result is a tumor, a neurodegenerative disease or an infection, the greatest challenges facing humanity in the field of health.

He has been one of the most cited scientists in the world for almost a decade and his list of accolades is immense.

He leads the Bionanoplasmonics group at the CIC Biomagune research center in San Sebastián, is a professor at the University of Vigo, principal investigator at the Center for Network Biomedical Research, Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) and, this month, he will be awarded a PhD

from the University of Antwerp (Belgium).

Ask.

They say that their investigations are on the frontier of knowledge.

Answer.

All scientists aspire to that.

We seek to open new paths and resolve relevant questions that are not resolved and that may be of interest for other researchers to use and for it to reach society, which is the ultimate goal.

Q.

Do

to cells with nanomaterials?

R.

We work with nanomaterials made of noble metals, mainly gold, because at this size scale, nanometric, metals interact with light in a different way than they do at macroscopic size.

The colors we see are different depending on the size or shape of the particles we make.

Those colors, that interaction of light with the electrons of the metal, allow us to amplify a specific signal from the molecules that will later tell us how a tumor or bacteria or water contamination is working or gives us a label to avoid fakes.

Each molecule has a specific signal in Raman spectroscopy, and if we can see that signal sensitively enough,

we can know if the molecule we are looking for is present and how it is changing over time or what processes are taking place.

This is something that, in the case of tumors, makes it possible to study metabolic processes of metabolite conversion, which happens differently in tumor cells than in healthy cells.

That is what gives us the ability to know what cells are saying to each other in order to expand or kill the tumor or whatever we are studying.

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Q.

Would it allow us to know the most initial stages of a tumor to advance in early diagnosis?

A.

It has several advantages.

Ex vivo [outside the body] analysis of a biopsy can be done relatively quickly and, moreover, the instrumentation required could even be simplified, without too expensive or complicated resources.

But it also has its problems and that is why it is not being used yet.

It is something that we and many more scientists in the world are investigating: that the signals that are seen can really be distinguished perfectly from others that may come from other substances that are in the same medium and, furthermore, that we can tell in a very reliable way How much of each substance do we have?

For this, we are beginning to apply artificial intelligence techniques to analyze the data we obtain.

Q.

Do you mean that there are imposter cells?

A.

Not necessarily.

Imagine taking a blood sample, removing the red blood cells, and drawing the serum.

In that serum there are still proteins, lipids, salts and many substances that can also give a signal in Raman spectroscopy.

We need to make sure that the signals we see when we measure tell us that what we are looking for is present or not.

In order to know this in an indisputable way and for the diagnosis to be reliable, we need to understand very well what are the signals that come from what is always there or from what is usual and what are the signals that really indicate whether the diagnosis is positive or not. negative.

We are recently in the development of

, which can be handled in the laboratory, the most similar to real tumors.

For this, we use 3D bioprinting techniques that generate models that contain all the elements of tumor cells, of the healthy cells that are usually around them, and of the components of what is called the tumor microenvironment.

These can allow us, for example, to evaluate the efficacy of drugs for a certain type of tumor.

The idea is to do this with cells derived from patients to try to do an

of the efficacy of drugs, without the need for animal experimentation, and, if everything goes very well, contribute to personalized medicine, studies of the efficacy of drugs for a specific tumor of a specific patient to, from there, guide the clinician in administering the therapy.

It is our ambition, our dream for the future.

We are going to have a meeting with specialist collaborators in the cancer molecule to design the next steps in this direction.

We use 3D bioprinting techniques that generate models that contain all the elements of tumor cells, of the healthy cells that are usually around them, and of the components of what is called the tumor microenvironment.

Q.

Would this reconstruction of the characteristics of a tumor also allow us to know what its evolution would be?

R.

It is early to say.

We have to see how to find the conditions so that, effectively, these models have a sufficient life to be able to monitor them over time, under conditions that are sufficiently realistic.

It takes time.

The record we have is great and the collaborators we have, too.

But everything takes time and, when working with biological systems, research is much slower.

It must be done very carefully, being sure of what is being done and with all the necessary controls.

Q.

What are nanostars like?

R.

One of the types of materials we make is called a nanostar because it's like stars on Christmas trees, many points but nanometer in size.

One of the jobs with the greatest impact that we have done in our group over the years is the synthesis, the manufacture of these nanomaterials, using chemical methods with great precision so that we can control the size and also the geometry of the particles. what do we need.

Right now we have a library with spheres, cylinders, triangles, cubes, octahedrons... Each of these geometries has a characteristic that makes them special and suitable for an application.

One of the applications that are already in clinical trials in the United States is the ability to kill cells selectively and that is being tried to apply to tumor therapy as well.

This is based on the fact that when we illuminate these particles with a laser light of a certain color, in addition to the ability to identify molecules, it can also heat what is around that particle.

If we can selectively place the particles on harmful cells and shine a suitable laser to produce heating of the particles, but without affecting the surrounding tissue, then we can selectively destroy tumor cells.

The efficiency of that process depends on the geometry and size of the particle.

If we can selectively place the particles on harmful cells and shine a suitable laser to produce heating of the particles, but without affecting the surrounding tissue, then we can selectively destroy tumor cells.

The efficiency of that process depends on the geometry and size of the particle.

If we can selectively place the particles on harmful cells and shine a suitable laser to produce heating of the particles, but without affecting the surrounding tissue, then we can selectively destroy tumor cells.

The efficiency of that process depends on the geometry and size of the particle.

Q.

Could it be applied without intervening in the patient?

A. It

depends.

There are tumors that are relatively well located and not too far from the skin, such as breast tumors or melanomas, where nanoparticles, which are normally dispersed in water, could even be injected.

And once they have accumulated in the corresponding area, which can be favored by placing selective antibodies on the nanoparticles to recognize tumor cells, the laser could be used without opening.

If we can selectively place the particles on harmful cells and shine a suitable laser to produce heating of the particles, but without affecting the surrounding tissue, then we can selectively destroy tumor cells.

Q.

Can it also be used in neurodegenerative processes?

R.

We have studied in this direction, although it is still a bit green.

We have done work that needs continuation and specific funding.

What we have done is look for a different way of using gold nanoparticles to see the evolution in the formation of amyloid fibers, which are the aggregates of the proteins of the same name and which are related to neurodegenerative processes.

We have detected signals in samples derived from brains supplied by the biobank and they were different if they came from people who had suffered from Parkinson's disease or from another person who died from another disease unrelated to these degenerative processes.

But we still haven't gone much further in that direction because we don't have the material time or adequate funding.

Q.

And could nanomaterials be used in infectious processes?

R.

_

We use similar techniques to, in this case, listen to how bacteria talk to each other.

This is related to certain molecules that the bacteria release or recognize with certain membrane proteins.

With this you can know how many bacteria they have around.

It is a mechanism known as

that is to say, that the bacteria, with this form of communication, can know if in their colony they have

to carry out a certain function.

We can detect very low concentrations, in the initial stages of communication, and even study

without affecting the behavior of the bacteria, how the presence of one type of bacteria affects the processes that take place in a different bacterial family placed a few millimeters apart.

The ability to detect bacterial growth with these methods is very good.

We are continuing research in this direction.

Q.

Do you mean that they spy on the bacteria to find out their intention?

A.

That is.

For detection, we try to listen to them without them knowing that we are there because if they detect that there are foreign objects, they could act differently.

But if we wanted to affect them, we could add nanoparticles, illuminate them with the laser and also perform that function of heating and destruction.

In this we must be careful because, although we know that the particles we work with are not toxic, whenever the possibility of exercising a therapeutic function by injecting nanoparticles is considered, other aspects must be taken into consideration, such as, for example, what happens with those nanoparticles after doing the therapeutic function.

Q.

Are there side effects in the application of the laser with nanoparticles?

R.

Depending on the intensity of the laser, unwanted processes could be generated within the body.

It is something that we study in detail.

We can regulate the lighting conditions necessary to heat it up enough to kill the cells you want to destroy, but without going overboard, so there aren't those side effects.

On the other hand, there remains the question of what happens to nanoparticles that are not normally in the body.

You have to see if he can release them or if they can be released in a low enough quantity so that, even if they stay there, nothing happens.

We have been using gold nanoparticles for diagnosis since the 1960s and, in the last two years, we have used them in practically the entire population in antigen tests,

where the lines that indicate whether the test is positive or negative are due to the accumulation of gold nanoparticles that carry the specific antibodies to recognize the antigens.

Also in pregnancy tests, which use gold particles to detect the presence of the characteristic hormone of pregnancy.

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