PSi hits the spot

Hélder Santos’ research group is developing medicines of the future through microflows.

University researcher Hélder Santos leads a multicultural team on the Viikki Campus. Of the nearly two dozen researchers in the "Santos Lab” studying targeted drug delivery, only one is a native Finn. The rest are from China, India, Spain, Italy, Russia, Thailand and Iran, as well as Santos’ native country, Portugal.

“I try to keep all of them motivated. When people feel like they are among friends, they’re not afraid to ask for help," Santos says.

Santos usually tries to involve the whole group in discussions. If somebody has a problem, another member of the group may have a solution. Social activities, such as go-karting, canoeing and barbeques also help build team spirit.

Thanks to successful motivation – or successful recruitment – the group is riding the crest of the nanomedicine wave. Group members are using a variety of approaches to study drug delivery methods – how an active compound can be packaged so that it makes its way to the correct location in the body and penetrates the necessary cell.

Silicon particles

In Santos’ research, nano-sized precision capsules are manufactured using a technique known as microfluidics. A steady flow of porous silicon, or PSi, particles carrying water, ethanol, polymers and drugs, is fed through two channels into a tiny glass capillary tube.

In these controlled microflows, the PSi particles are also coated with a layer of polymers.

It is possible to add drugs to the flow itself. The end result will be a polymer-covered PSi particle which contains one type of drug and has another, or even two others, in its coating. This way, drugs which cannot be in contact with one another can be compiled into a single nanoparticle.

“We are currently working on nanoparticles which can contain several different drugs for combination therapy in heart attacks. This is the only way we can make sure that the drugs really enter the heart simultaneously.”

PH is the key

Santos’ research group has tried several different methods to ensure the PSi particles carry the drugs to the right destination. One common method is to manipulate how well the polymer coating can tolerate acidity.

For example, cancer drugs are wrapped in a polymer shell which will only dissolve in high acidity. Such PSi particles injected into the bloodstream will circulate in the body through the vascular system (pH 7.4) and healthy cells (pH 7), but its coating will dissolve inside a cancerous cell (pH 4-5), Santos explains.

Accuracy is improved by adding “seeker molecules” to the polymer coating – these molecules are precisely modified to recognise their target in the cell and bind with it, letting the particle enter the cell.

Most of the time, PSi particles are injected into the bloodstream, but for the treatment of diabetes, Santos' team is developing insulin-carrying nanoparticles which can be administered orally.

“Instead of constant injections, a diabetic could take one pill every week or two.”

The stomach is a highly acidic environment, but in the small intestine, pH levels can be as high as eight. This means that orally administered PSi particles must be covered with polymers which tolerate high acidity but dissolve in neutral or alkaline environments.

In the small intestine, the PSi particles are released and then firmly attach to the intestinal wall with the help of their seeker-molecules. They then begin to slowly release insulin through the membrane into the bloodstream.

 “In the future we will even be able to programme the particles so that they administer insulin on a specific schedule."

Long, slow road

In the laboratory, these smart silicon particles are yielding excellent results. However, medicine’s PSi revolution is still a long way from the corner pharmacist’s or local hospital’s supply closet. 

The PSi drugs developed by the Santos team have so far only been tested on animals, mainly mice and rats. At the moment, PSi drugs are not on the market anywhere in the world, even though they may soon be used in the treatment of liver and pancreatic cancers.

Pharmaceutical safety protocols are particularly strict for the use of porous silicon, as regulators must evaluate the safety of the carrier particle and the drug both separately and together.

“It can easily be 20 or 30 years before these drugs hit the market. By that time we will have developed better treatments, but they, too, must go through the same application processes.”

Drug discovery can be frustrating.

“It’s important to ensure safety, but some patients will die because new, improved drugs are not available to save them.”

Science and love

Many top researchers have wound up building a career in Finland because they have fallen in love with a Finn. Santos' Finnish wife is also a researcher, and the couple drive from Riihimäki to Viikki every day.

Santos emphasises, however, that when he arrived in Otaniemi as a doctoral student in 2003 he came purely out of a love for science. Finland offered a faster career track for a young researcher than Portugal, and the Department of Chemical Technology at the Helsinki University of Technology happened to have exactly the equipment that Santos needed for his research interests.

 “I met my wife when I was already working in Finland. She was studying the nanosystems that transport genes into cells. This introduction to pharmacy encouraged me to become a postdoctoral researcher in Viikki.”

Also read the article “Chasing a precise pill” in this issue.

This article was published in Finnish in the Y/08/16 issue of Yliopisto magazine.