Tiny but deadly: four nano cancer-killing weapons
Tumours are tricky – they're able to hijack surrounding tissue to grow and spread, yet hide from our immune system. So scientists have engineered drugs and delivery systems to target cancers while keeping normal tissue safe. Viviane Richter reports on four of the most promising.
Sometimes big problems call for tiny solutions. And one solution that gives hope to the 14 million patients facing a cancer diagnosis each year is nanomedicine.
Scientists have engineered sub-microscopic delivery vessels, each so small a thousand lined up would barely span the width of a human hair, to give cancer drugs or other treatments more power, while reducing nasty side effects to normal cells.
The field is flourishing, with as many as 1,381 nanomedicine cancer therapies registered for clinical trials in December 2014.
Here are four top strategies from the research frontline, with some that have already made a difference for patients.
Therapy gone viral
Viruses generally get a bad rap. But in the early 1900s, doctors noticed some cancer patients went into remission following a viral infection, which inspired a new field in cancer therapy.
Scientists discovered some viruses prefer to infect cancer cells over normal cells. The infected cells burst and release molecules which rile up the body’s own immune system to attack other cancer cells.
Scientists have engineered these “oncolytic” viruses to boost their attacking power. One example is the herpes simplex virus 1 that causes cold sores, which has been genetically altered to produce drastically fewer herpes symptoms, but stimulate the immune response even more. The resulting “T-VEC” virus has been successful in clinical trials, shrinking tumours and extending survival rates in advanced melanoma patients.
In October 2015, the US Food and Drug Administration (FDA) approved the use of the genetically engineered virus T-VEC for the treatment of advanced melanomas. The European Commission followed suit in January this year, which experts believe paved the way for many more oncolytic viruses in the clinical trial pipeline.
“The era of the oncolytic virus is probably here,” Rochester Mayo Clinic cancer researcher Stephen Russell told Nature. “I expect to see a great deal happening over the next few years.”
Antibodies are immune system molecules that recognise molecules of invading pathogens.
But scientists have cooked up antibodies in the lab which recognise and latch on to cancers. Attaching them to drugs turns them into guided missiles locked on a cancer target.
When zapped with short bursts of infrared laser, gold particles heated and vapourised the surrounding liquid, creating tiny bubbles which tore cells apart.
An example approved for use by the FDA in 2011 and already in the clinic is Adcetris, which delivers a cancer drug to receptors called CD30 on Hodgkin lymphoma cells. Similarly, Kadcyla targets a toxic drug to the HER2 receptor of breast cancer cells and was FDA-approved in 2013.
Recently, scientists from the US and Belarus published a different approach. They attached antibodies to gold nanoparticles, designed to seek out and blow up rogue cancer cells left behind after surgical removal of aggressive tumours.
Why gold? When zapped with short bursts of infrared laser, gold particles heated and vapourised the surrounding liquid, creating tiny bubbles which tore cells apart. But gold particles sporting cancer-recognising antibodies targeted tumours, the authors discovered in mouse experiments, reducing damage to normal cells.
They found the method improved survival rates of mice with head and neck cancers two-fold in cases where only partial removal of the tumour was an option. The team is currently designing a clinical trial which could see their gold particles tested in humans in the next two years.
Taking a hot iron
German biotechnology company MagForce has developed iron oxide nanoparticles they call NanoTherm, which quite literally cook tumours from the inside.
These particles, each a ten-thousandth the width of a human hair, are injected directly into a tumour. When the patient is then placed in an alternating magnetic field, the particles agitate and heat up, either destroying the cancer cells or making them more sensitive to other treatments.
NanoTherm has effectively treated glioblastoma brain tumours when used in parallel with radiotherapy. The treatment was approved in Europe in 2010 and is available in six German clinics.
Drugs as time bombs
Some cancer drugs are only effective when packaged up in nanoparticles made of molecule chains called polymers.
Breast and pancreatic cancer drug Abraxane, for instance, FDA-approved in 2005, contains an active ingredient isolated from the pacific yew tree which mixes poorly with water. It has to be knitted up in a protein nanoparticle to be effective when injected into patients.
Other drugs, such as the common cancer therapeutic cisplatin, accumulate more in tumours when stitched up in a polymer nanoparticle than if they were administered alone. This has also been shown to decrease the drug’s toxicity in phase 1 clinical trials.
And recently, a team of Chinese and US scientists developed a method for packaging drugs as polymer nanoparticles in a way that let tumours activate their own time bomb.
They laced porous silicon particles with the drug doxorubicin, packaged as inactive polymer chains. When injected into a tumour, the silicon broke down, slowly releasing the polymers which folded up into nanoparticles and accumulated in cancer cells. The active drug was only released when the particles reached acidic regions inside cancer cells, hitting the cells right at their core.
The team’s method has shown promise in mice implanted with an aggressive, metastatic triple negative breast cancer. Where doxorubicin alone prolonged survival by 19 days, 40% of mice treated with the drug packaged in silicon nanoparticles survived more than 180 days. The team is planning human studies in 2017.
“If this research bears out in humans and we see even a fraction of this survival time, we are still talking about dramatically extending life for many years,” said Mauro Ferrari of the Houston Methodist Research Institute, who was involved in the study.
“That's essentially providing a cure in a patient population that is now being told there is none.”