Nano Scouts
A specialized mini search party combs the body for tumors, attaches itself like a burr if hit, provides doctors with a reliable light signal, blocks the supply transport routes for the degenerated tissue and also takes care of it with a drug in the luggage for a first stroke against cancer - a dream? Still yes. But the reality is getting closer.
Do you remember the classic film "The Fantastic Voyage"? In it, a submarine and its crew are shrunk to the size of a microbe and injected into the bloodstream of a defected diplomat. The team has one hour to remove a blood clot in the man's brain using a laser beam. Some things in the strip may seem hopelessly outdated these days, but the idea – to unleash a specialized, independently operating search and attack squad on bodily internal adversities – is still science fiction. But she's nowhere near as wacky as she was forty years ago when the film was made.
The work of Erkki Ruoslahti at the Cancer Research Center of the Burnham Institute for Medical Research in La Jolla and his colleagues are reminiscent of the original film. Well, they do without the miniaturized crew - which they don't even need. Because the scientists have put together nanoparticles from various components that independently detect tumors and at least make them more visible.
The actual tracker is a peptide with just five amino acids: cysteine, arginine, glutamic acid, lysine and alanine, or creka for short. Ruoslahti and his colleagues provided this short protein molecule chain with a fluorescent dye and injected it into mice with cancer. The team discovered traces of light only inside the tumor and the supplying blood vessels – but not in he althy tissue. The researchers discovered that the peptide is particularly enthusiastic about clumped plasma proteins: no telltale traces of color were found in genetically modified mice that cannot produce the necessary fibrin. Because these clumps are typical of tumors, they make excellent targets.
In the next step, the researchers attached their signaling scout to nanoparticles made of superparamagnetic dextran-coated iron oxide (SPIO) - a contrast agent used in magnetic resonance imaging. In cell cultures, the particles still bound tightly to clumps of protein present, so the first test for use as a nano-submarine on a special mission was passed.
But like in the film, such a foreign body in the bloodstream naturally has to contend with massive resistance. Immune system patrols who encounter the intruder will try with all means to render the suspected enemy harmless - in the case of the nanoparticles simply eat them up. Which is what happened when the scientists injected their construct into live mice.
There was only one common distraction: decoys. Before injecting their animals with the tumor scouts, the researchers treated the mice with liposomes that they had coated with nickel. This kept the rodents' immune defenses so busy that not only did the half-life of the circulating nanoparticles increase fivefold, but their hit-binding rate also increased. However, the success is marred by a worrying downside: some mice did not survive this pretreatment. Without nickel, however, the liposomes proved to be significantly less effective. "Reducing the nickel content could represent an appropriate compromise between toxicity and effectiveness," the researchers speculate. So there is still some tinkering to be done here.
But they were happy about another, unexpected effect: The nanoparticles not only bind to clumps, they also clump together. On the one hand, this amplifies the light signal, but on the other hand, it also clogs the colonized vessels. So far, the search parties have only cut off a fifth of the tumor's supply routes in this way, which does not slow it down further in its growth. However, Ruoslahti and his team believe that this campaign could certainly be spurred on – after all, starving out tumors by cutting off the blood supply that supplies them is one of the most important approaches in cancer treatment. And that is by no means the end of all the possibilities: the scientists hope that the nanoparticles could be strapped on to a drug piggyback that would attack the tumor chemically.
So is medicine coming up with the fantastic journey, episode two, to cancer therapy? Of course not that quickly. Quite apart from the fact that all studies so far have been made on mice, not humans, the main question remains about the risks and side effects. As nice as the whole plot reads, there are a few points in the results that need to be examined more closely. For example, the researchers found their nanoparticles in high concentrations in the liver. Although they did not clump together there, it is still unclear whether they harmed the animals in the long term or in some other way. It also remains to be clarified to what extent the particles are deposited with adverse effects in other organs or body regions - such as open wounds, for example, which also offer a rich supply of plasma protein clusters.
So the signaling license-to-kill tumor nanoscout is still science fiction. But what will we say about that in forty years?
