European Inventor Award

Fighting cancer with nanotechnology

Patrick Couvreur

Winners of the European Inventor Award 2013 in the category Research

Patrick Couvreur, Barbara Stella, Véronique Rosilio, Luigi Cattel, inventors of nano-capsule cancer medicines

In the fight against cancer, scientists have long dreamed of a ‘magic bullet' to eliminate diseased cells without harming healthy tissue. This dream became reality when nano-capsules that deliver potent anti-cancer drugs directly to tumour sites entered clinical practice.

The revolutionary method is based on breakthrough discoveries patented by Belgian-born nanotechnology pioneer Patrick Couvreur, Professor and Director of the Physical Chemistry, Pharmacotechnology and Biopharmacy Unit at Paris-Sud University in France.

Treating a top killer

Laboratory Despite advancements in treatment, cancer remains one of the leading causes of death worldwide. And it's getting worse: In the year 2030, researchers from the International Agency for Research on Cancer (IARC) expect 22.2 million new cases of cancer worldwide, a 75% rise from 2008.

Chemotherapy, the treatment of cancer with toxic chemicals suppressing the multiplication of diseased cells, is one of the main weapons against the disease.

Chemotherapy had its start in the early 1900s, and its underlying principle has always remained the same: The aggressive chemicals trigger the death of fast-dividing cells such as the ones involved in cancer.

But chemotherapy's side effects can be devastating because it doesn't only harm tumours but can also wreak havoc on healthy cells in the patient's liver, digestive tract and bone marrow. And the right dosage is key: The difference between poison and cure was often in the realm of a few milligrams.

“Pharmaceutical companies are extremely aware of a clear and focused patent situation before investing into development or production.”

A ‘magic bullet' for targeting cancers

Looking for an alternative, the ‘father' of chemotherapy, 1908 Nobel Laureate for Medicine Paul Ehrlich, envisioned a more controlled way of killing diseased cells. The pioneer dreamed of drugs that would hit home like magic bullets, called ‘Zauberkugeln' in German - never missing their intended target.

The magic bullets remained a dream until the year 1977, when nanotechnology pioneer Professor Peter Paul Speiser met young researcher Patrick Couvreur at the ETH (Swiss Federal Institute of Technology) in Zurich.

Together, the two pursued the fundamental principle of today's nano-medicines: By sealing the active ingredients inside nano-capsules - miniature materials that gradually break down after injection - the drugs take effect in a prolonged, more controlled manner. Adverse side effects are also reduced.

The long road to scientific breakthroughs

In 1979, Couvreur succeeded in encapsulating medicines in biodegradable nano-particles, making them fit for use in humans - in theory, at least.

To keep things moving, Couvreur took his research to Paris-Sud University, where he assumed key responsibilities as a researcher and coordinator between academics and the pharmaceutical industry.

In order to carry out clinical trials of his invention, Couvreur founded Paris-based BioAlliance company in 1997. One initial challenge was to scale up the production of nano-particles: "During laboratory research, we were working with milligrams, for the clinical phase we needed kilograms," Couvreur said.

Securing a European patent was also key in getting the new company off the ground: "Pharmaceutical companies are extremely aware of a clear and focused patent situation before investing into development or production," Couvreur said.

“At the moment, we are already able to optimise the ratio of drug transporter and drug agent by 50 times. Let’s see where we will stand in a few years.”

Bridging the gap between research and practice

LaboratorySince its founding in 1997, Couvreur's company BioAlliance Pharma has raised €20.8 ($27.0) million from financial and strategic investors. Current results are highly promising:

"At the moment, we are already able to optimise the ratio of drug transporter and drug agent by 50 times. Let's see where we will stand in a few years," Couvreur  said. 

The pioneer's nano-medicines are especially suitable for the treatment of pancreatic cancer, a drug market expected to exceed $1.5 billion by 2015. In Europe, pancreatic cancer is the 10th most frequent cancer type, accounting for 2.6% of cancer in both sexes, and the eighth leading cause of cancer-related death, with approximately 65,000 deaths each year.

"We are attacking other diseases. One important disease is HIV. Our first tests were extremely encouraging that our nano-capsules will also increase the efficiency of drug delivery for HIV treatment," said Couvreur.

Dreaming of a ‘drug discovery institute'

Constantly striving to see medical breakthroughs all the way into clinical practice, Patrick Couvreur cofounded the Therapeutics Innovation doctoral school at Paris-Sud University, where he was from 1998 to 2010 director of the Physical Chemistry, Pharmacotechnology and Biopharmacy Unit with a team of 110 researchers.

"My real dream is to develop an effective anti-cancer medicine and to create a 'drug discovery institute' in the Ile-de-France region, to give France international visibility in this field," Couvreur said.

A lifetime of dedication to research

Together with his research team at start-up company Medsqual, Couvreur is currently working on the third generation of nano-particles. It combines the anti-cancer drug Gemcitabine with the compact lipid squalene for a ten-fold increase in effectiveness on tumours. The new drug was patented in 2011 and is now undergoing Phase III clinical trials, with expected approval by FDA and EU regulators by 2015/2016.

With his dedication to research and constant lobbying in the pharmaceutical industry, Patrick Couvreur has played a key role in fulfilling the dream of magic bullets envisioned by pioneer Paul Ehrlich more than 100 years ago.

How it works

The nano-particles invented by Patrick Couvreur measure between only 10 to 1,000 nanometres and are free to travel throughout the body without being absorbed or dissolved like conventional drugs injected into the bloodstream.

Instead of releasing their biologically active ingredients right after injection, the drugs inside nano-capsules only deliver their load after the outside coating has dissolved, either because of changes in temperature or of chemical factors such as the biological breakdown of fats in certain body regions.

As a result, nano-capsules offer a much longer half-life in the bloodstream compared to conventional injections, and they can take effect in a much more concentrated, spatially condensed fashion.

Another advantage of covering drugs with polymers lies in the fact that the human immune system does not recognise the drug before the coating is dissolved. Together with their small size, this ‘stealth' coating enables drug-laden nano-particles to travel throughout the body, even crossing the blood-brain barrier.

Science fiction, nano-robots and ‘remote-controlled' drugs

Before it advanced into a billion-dollar market (expected to exceed $30 billion by 2015), nanotechnology was the stuff of science fiction movies. In the 1966 film Fantastic Voyage, a team of researchers is shrunk to nano-dimensions and injected into a person's blood stream. Medical schools would screen the film to illustrate concepts of immunology.

Today, researchers are fervently pursuing the construction of nanorobots, tiny machines at a scale between 0.1 and 10 micrometres. In the future, these micro-machines could be injected into patients to fulfil a number of tasks, from diagnostic surveys to the repairing of cells all the way to nano-surgery.

Another cutting-edge approach to controlled drug delivery lies in the combination of nano-particles with magnetic nano-crystals, which can be ‘remote-controlled' via high-resonance magnetic fields to targeted locations inside the human body.

Potent anti-cancer drugs are in higher demand than ever before. Cancer is currently the leading cause of death worldwide, and the World Health Organization estimates its toll to rise to 13.1 million in 2030.

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