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Disease and treatment

Gold brings the dream of more targeted cancer drugs closer to realization

Danish researchers have shown that they can use gold nanoparticles to precisely target the delivery of medicine directly to where it is needed. In the future, gold nanoparticles may help in delivering more potent chemotherapy, for example.

For many years, doctors have dreamed of being able to develop more targeted treatment of diseases such as cancer.

For example, tumours are treated with chemotherapy. The current treatment method affects and damages not just the tumour but the entire human body. Naturally, doctors would much prefer to target the tumour alone because they could use much more potent forms of chemotherapy without the risk of killing the patient.

The dream of finding a method of targeting a tumour much more precisely while leaving the rest of the body untouched is now a step closer. This advance is based on Danish researchers showing that, upon laser irradiation, gold nanoparticles can release medicine very precisely where it will have the greatest effect.

“The goal is to be able to use drugs that are so powerful that they can easily kill the tumour and yet make the treatment so localized in the body that the patient does not die. By developing this method based on laser irradiation of gold nanoparticles, we have taken a step towards being able to deliver a very targeted and local release of medicine inside the patient,” explains Lene Oddershede, Professor, Niels Bohr Institute, University of Copenhagen.

The study was published recently in Langmuir.

Laser-activated gold nanoparticles release drugs

The mechanism that enables the precise delivery of medicine from gold nanoparticles is that they heat up when exposed to near-infrared light of a specific wavelength. If researchers load various molecules on gold nanoparticles, such as tiny fragments of double-stranded RNA, some or all of these molecules will be released when the gold particles are irradiated with a laser.

In a hypothetical treatment situation, the gold nanoparticles coated with an anti-cancer drug would be infused into a patient’s bloodstream. Based on the structure and nature of the vascular system in tumours, gold nanoparticles of a specific size would be concentrated in the tumour. If doctors irradiate the tumour with near-infrared light, the cancer drug would be released very precisely at the location at which it can cause the most damage to the tumour.

The rest of the body would not be affected by the medicine to the same extent, and doctors can therefore use more potent anti-cancer drugs in treatment. This also includes anti-cancer drugs that are so powerful that they cannot currently be used to treat people.

“This is very smart; since tumours grow so rapidly, their blood vessels are also more brittle and porous. This means that, because of their size, the gold nanoparticles can penetrate the membrane of the blood vessel and move into the tumour cells – like small Trojan horses. Subsequently irradiating the tumour with a laser directs the near-infrared light through the body onto the gold nanoparticles. The heat induces the drug release,” explains Lene Oddershede.

The researchers had carried out studies on mice showing that the gold nanoparticles could be concentrated in the tumour. Solely heating the gold nanoparticles can actually make a tumour smaller or make it disappear completely. However, it will still be beneficial to develop a treatment that combines both heating and the release of a highly potent anti-cancer drug.

Evidence that the system works in cell cultures

In the new study, the researchers carried out experiments using cell cultures. This showed that their system has potential.

First, the researchers got tiny fragments of RNA to stick to tiny spherical gold nanoparticles with a diameter of 100 nm. The gold bullets ended looking like tiny pin cushions, with RNA sticking out from all sides.

Then the researchers added the gold bullets to a cell culture, and the cells absorbed the gold bullets in a process called endocytosis. The researchers then irradiated the gold bullets, causing the double-stranded RNA to melt, with one part of the RNA strand detaching and being released inside the cell. This is the main result of this new study.

“By permanently attaching a fluorescent molecule onto one of the RNA strands, we can see under a microscope how the RNA is separated from the gold bullets and diffuses into the cell,” says Lene Oddershede.

Gold nanoparticles can distribute all types of medicine

The researchers’ experiments with getting RNA to attach firmly to the gold particles was no accident.

Tiny fragments of RNA can act as very potent medicine against such diseases as cancer because the RNA can attack the RNA of the cancer cells and, for example, inhibit the growth of the tumour or activate cell death.

“Our study shows that we can attach any type of RNA onto the gold nanoparticles, so there is every reason to believe that we can do the same for any type of medicine such as taxol chemotherapy, which is used to treat many types of cancer today. Our system enables taxol chemotherapy to be directed right into the tumours, enabling the drug to do maximum damage without being distributed to other locations,” says Lene Oddershede.

The next step for the researchers is experiments using an animal model, attempting to replicate the results from the cell cultures. The researchers will see whether they can use this method to deliver specific molecules into the tumour – without affecting the rest of the mice’s bodies. Currently, however, these studies are still on the drawing-board.

Quantification of Loading and Laser-Assisted Release of RNA from Single Gold Nanoparticles” has been published in Langmuir. In 2014, the Novo Nordisk Foundation awarded a grant to Lene Oddershede for the project Laser activated nanoparticles for tumor elimination, Acronym: LANTERN.

Lene B. Oddershede
Professor
Lene B. Oddershede is group leader of the Optical Tweezers Group at the Niels Bohr Institute, University of Copenhagen. Recently, she became the PI of an inter-disciplinary Danish Grundforskningsfond Center of Excellence, StemPhys, which has a focus on stem cell decision making and will run from 2015 until 2021. The main research interests of Lene B. Oddershede are on the boarderline between physics and biology, where she investigates physical properties of biological systems at levels ranging from the single molecule to the whole cell. Also, she has a sincere interest in nanoparticle plasmonics. The labs of LBO have available state-of-the-art force-scope optical tweezers, single particle tracking, and fluorescence techniques, also subdiffraction.