Destroying tumors with gold nanoparticles

File 20180615 85834 19fjytg.jpg?ixlib=rb 1.1
Section of a tumor observed with an optical microscope. The two white forms with brown borders are blood vessels. Inside, gold nanoparticles accumulate against their walls.
Mariana Varna-Pannerec (ESPCI), Author provided

By Emmanuel Fort, ESPCI Paris

Gold has extraordinary properties. It can be used to make jewelry, but also to fight cancer. Several clinical trials are currently underway in the United States where patients are being treated with gold nanoparticles.

In its natural state, gold is a yellow, chemically inert, non-corrodible metal, making it a noble material that does not degrade over time. These properties, along with the ease with which it can be shaped, have made it the favourite metal of jewellers.

On a nano-metric scale – that is, at a millionth of a meter – gold has other remarkable properties. On this scale, gold particles take on various colours according to their shape and size. This property has been used since ancient times to colour glass and earthenware – giving them, for example, an intense ruby hue. When light is shone on gold nanoparticles, the metal’s conduction electrons are excited by the light wave and begin to oscillate. This oscillation is particularly intense for a given colour in the light spectrum. This is called resonance.

The Roman cup of Lycurgue, from the 4th century. When illuminated from the inside, a beautiful ruby colour appears, coming from the gold and silver nanoparticles contained in the glass.
Trustees of the British Museum
Here the same cup, without interior lighting.
Trustees of the British Museum., CC BY-NC-SA

By changing the shape or size of the nanoparticles, it is possible to choose the resonance frequency that has the strongest interaction with light. The nanoparticles then behave like tiny, highly effective antennae, and although they are extremely small and highly diluted they can give vibrant colours to stained glass.

One incidental consequence of this intense interaction with light is that nanoparticles heat up. This remarkable property is the reason behind their use in new cancer therapies. The idea is to destroy the tumours with photothermia – in other words, to locally heat up tumours “decorated” with gold nanoparticles by exposing them to light.

Patients being treated this way are first injected with gold nanoparticles into their bloodstream through an IV. Since gold is biocompatible, it presents no apparent danger to health in the concentrations used in therapy, as borne out by our studies in mice. However, not all questions have been resolved concerning these new applications. Gold nanoparticles go undetected by the body’s immune defence system. Their nanometric scale means they are generally one hundred times smaller than cells, allowing them to move freely through the blood system and enter the tumour.

They must then be concentrated inside the tumours, many of which are highly vascularized – they naturally acquire a network of blood vessels allowing them to grow. Using this pathway, the nanoparticles easily accumulate inside the tumour. The altered structure of the blood vessels in the tumour area makes them more permeable, facilitating a high retention of nanoparticles.

Tumours “decorated” with gold nanoparticles are then exposed to light, in order for them to heat up and be destroyed. At this stage, the challenge is twofold. While the light must penetrate the body and reach the tumour, healthy tissue must not be heated. The choice of frequency is therefore vital. Nanoparticles must be lit up at their resonance frequency, but it is just as essential that the tissues without nanoparticles not absorb the light.

While our bodies absorb light in the visible part of the light spectrum (that is, all the colours of the rainbow), this is not the case in the near infrared. We can see this by simply placing a hand over an intense white light. Only the colour red, on the edge of infrared, can move through the flesh of the hand.

This range of the spectrum in the near infrared is often called the “therapeutic window” – the range that can be used in medical treatment. In the visible spectrum, light is mainly absorbed by hemoglobin, while light further into infrared range is absorbed by the water contained in our bodies.

Gold nanoparticles are injected into a mouse carrying a tumour. Five hours later, sections of the tumour are examined through an optical microscope (centre). We can see the gold nanoparticles
Mariana Varna-Pannerec (ESPCI), Author provided

Nanoparticles with specific shapes

By playing with the shape of nanoparticles, it is possible to adjust their resonance so as to target the near infrared therapeutic window. This is carried out, for example, for nanoparticles with a silica core and a gold shell, for gold nanorods, or for nano-cages shaped like porous cubes. Preclinical studies (in animals) have enabled us to test the safety and effectiveness of various shapes of nanoparticles.

In the therapeutic spectrum, light goes through our bodies, but our bodies are not totally transparent to it. The light that comes out the other side is still highly diffused by the body’s tissues. For instance, one cannot see bones in this way, as you would with an X-ray. It is also very difficult to focus a beam of light on a tumour from outside the body, since the light must travel through healthy tissue to reach it.

It is therefore usual (in animal studies) to light up tumours more closely, by inserting a needle through the skin, attached to an optical fibre linked to an infrared laser. The light is then far more intense in the relevant area.

Studies underway on head and neck cancers

Under the light, the gold nanoparticles heat up and “cook” the tumour, thus destroying nearby cancerous cells. Extensive studies have been carried out in animal models on cancers in the brain, prostate and pancreas, for example. Clinical trials are also underway in the United States in patients affected by treatment-resistant head- and neck cancers, and lung- and prostate cancers using AuroLase therapy (Nanospectra Bioscience).

Alternatively, nanoparticles can be used not as a direct weapon against the tumour but as a means of transport (called a vector) to deliver molecules – drugs, for instance – to their destination. This technique requires less heating. The use of vectors should reduce the toxicity of treatments by better targeting cancerous cells.

The Trojan horse strategy

It is possible to increase the number of gold nanoparticles entering a tumour, above and beyond the effect of simple passive accumulation. They perform better when covered with molecules (antibodies) that specifically attach to cancerous cells, which they recognize through the proteins present on the cell membrane. Other alternative techniques adopt a “Trojan horse” strategy. These use a kind of white blood cell, called microphages, filled with gold nanoparticles in order to penetrate more deeply into the tumour.

Gold nanoparticle photothermia is a promising new therapy in cancer treatment. It has begun to be used experimentally in patients with certain specific cancers, but much research is still necessary before it can be adopted more widely. In the future, the technique will have to target the tumour more effectively and exclusively. With thriving research, this therapy should be available, alongside existing treatments like radiotherapy and chemotherapy, in a few years’ time.

Created in 2007, the Axa Research Fund supports more than 500 projects worldwide led by researchers of 51 nationalities. Discover the work of Emmanuel Fort and his Axa ESPCI chair in biomedical imaging as part of the Axa Research Fund.

The ConversationTranslated from the French by Alice Heathwood for Fast for Word

Emmanuel Fort, Professeur de ESPCI Paris, Chaire AXA imagerie biomédicale, membre de l’Institut Langevin, spécialiste de l’interaction onde-matière, ESPCI Paris

This article was originally published on The Conversation. Read the original article.

Piercing the mystery of the cosmic origins of gold

Neutron Stars Rip Each Other Apart to Form Black Hole
“Neutron Stars Rip Each Other Apart to Form Black Hole”, NASA

Jérôme Margueron, University of Washington

Where does gold, the precious metal coveted by mortals through the ages, come from? How, where and when was it produced? Last August, a single astrophysical observation finally gave us the key to answer these questions. The results of this research were published on October 16, 2017.

Gold pre-exists the formation of Earth: this is what differentiates it from, for example, diamond. However valuable it may be, this precious stone is born out of mere carbon, whose atomic structure is modified by enormous pressure from the earth’s crust. Gold is totally different – the strongest forces in the earth’s mantle are unable to change the composition of its atomic nucleus. Too bad for the alchemists who dreamed of transforming lead into gold.

Yet there is gold on Earth, both in its deep core, where it has migrated together with heavy elements such as lead or silver, and in the planet’s crust, which is where we extract this precious metal. While the gold in the core was already there at the formation of our planet, that in the crust is mostly extraterrestrial and arrived after the formation of Earth. It was brought by a gigantic meteor shower that bombarded the Earth (and the Moon) about 3.8 billion years ago.

Formation of heavy elements

How gold is produced in the universe? The elements heavier than iron, including gold, are partially produced by the s process during the ultimate evolution phases of the stars. It is a slow process (s stands for slow) that operates in the core of what are referred to as AGB stars – those of low and intermediate mass (less than 10 solar masses) that can produce chemical elements up to polonium. The other half of the heavy elements is produced by the r process (r stands for rapid). But the site where this nucleo-synthesis process takes place has long remained a mystery.

To understand the discovery enabled by the August 17, 2017, observation, we need to understand the scientific status quo that existed beforehand. For about 50 years, the dominant assumption among the scientific community was that the r process took place during the final explosion of massive stars (specialists speak of a core collapse supernova). Indeed, the formation of light elements (those up to iron) implies nuclear reactions that ensure the stability of the stars by counteracting contraction induced by gravity. For heavier elements – those from iron and beyond – it is necessary to add energy or to take very specific paths, such as the s and r processes. Researchers believed that the r process could occur in ejected matter from the explosion of massive stars, capturing a part of the released energy and participating to the dissemination of material in the interstellar medium.

Despite the simplicity of this explanation, numerical modelling of supernovae has proved extremely complicated. After 50 years of efforts, researchers have just begun to understand its mechanism. Most of these simulations do unfortunately not provide the physical conditions for the r process.

These conditions are however quite simple: you need a lot of neutrons and a really warm environment.

Fusion of neutron stars

Two ounces of gold … from outer space.
Wikimedia, CC BY

In the last decade or so, some researchers have begun to seriously investigate an alternative scenario of the heavy-element production site. They focused their attention on neutron stars. As befits their name, they constitute a gigantic reservoir of neutrons, which are released occasionally. The strongest of these releases occurs during their merging, in a binary system, also called kilonova. There are several signatures of this phenomenon that luckily were seen on August 17: a gravitational-wave emission culminating a fraction of a second before the final fusion of the stars and a burst of highly energetic light (known as a gamma-ray burst) emitted by a jet of matter approaching the speed of light. Although these bursts have been observed regularly for several decades, it is only since 2015 that gravitational waves have been detectable on Earth thanks to the Virgo and LIGO interferometers.

August 17 will remain a major date for the scientific community. Indeed, it marks the first simultaneous detection of the arrival of gravitational waves – whose origin in the sky was fairly well identified – and a gamma-ray burst, whose origin was also fairly well localized and coincided with the first one. Gamma-ray burst emissions are focused in a narrow cone, and the astronomers’ lucky break was that this one was emitted in the Earth’s direction.

In the following days, telescopes continuously analysed the light from this kilonova and found confirmation of the production of elements heavier than iron. They were also able to estimate the frequency of the phenomenon and the amount of material ejected. These estimates are consistent with the average abundance of the elements observed in our galaxy.

In a single observation, the hypothesis that prevailed until now – of a r process occurring exclusively during supernovae – is now seriously under question and it is now certain that the r process also takes place in kilonovae. The respective contribution of supernovae and kilonovae for the heavy elements’ nucleo-synthesis remains to be determined, and it will be done with the accumulation of datum related to the next observations. The August 17 observation alone has already allowed a great scientific advance for the global understanding of the origin of heavy elements, including gold.

This NASA animation is an artist’s view and accelerated version of the first nine days of a kilonova (the merging of two neutron stars) similar to that observed on August 17, 2017 (GW170817). In the approach phase of the two stars, the gravitational waves emitted are coloured pale blue, then after the fusion a jet near the speed of light is emitted (in orange) generating itself a gamma burst (in magenta). The material ejected from the kilonova produces an initially ultraviolet light (violet), then white in the optics, and finally infra-red (red). The jet continues its expansion by emitting light in the X-ray range (blue)

A new window on the Universe

The ConversationA new window to the universe has just been opened, like the day that Galileo focused the first telescope on the sky. The Virgo and LIGO interferometers now make it possible to “hear” the most violent phenomena of the universe, and immense perspectives have opened up for astronomers, astrophysicists, particle physicists and nuclear physicists. This scientific achievement was only possible thanks to the fruitful collaboration between highly supportive nations, in particular the United States, Germany, France and Italy. As an example, there is only one laboratory in the world capable of reaching the required precision for the mirrors reflecting lasers, LMA in Lyon, France. New interferometers are under development in Japan and Indian, and this list will surely soon become longer given huge discoveries expected for the future.

Jérôme Margueron, Chercheur en astrophysique nucléaire, University of Washington

This article was originally published on The Conversation. Read the original article.