Nanoparticle "cluster bombs" could provide less toxic chemotherapy
Doctors have been using thechemotherapy drug cisplatin for decades, but significant toxic sideeffects – which can affect everything from the kidneys to theinner ear – limit its effectiveness as a treatment. A new method,which makes use of innovative nanoparticles, could change that,providing a "cluster bomb" approach to delivery that shows signsof being significantly less toxic to the patient.
The ongoing battle against cancer presents amonumental challenge for medical researchers, but potentiallysignificant breakthroughs are being made on a regular basis. Justthis week, scientists at the Brigham and Women's Hospital announcedthat they had successfully tested nanoparticles engineered to glow in the presence of dying cells, providing a real time indication oftreatment effectiveness.
Now, a collaborative team ofresearchers from the University of Science and Technology of China,Georgia Tech and Emory University, has also turned tonanoparticles, but with a very different goal in mind – to improvethe delivery of drugs to tumors.
Designed to deliver the chemotherapydrug cisplatin, the system makes use of tiny nanoparticles – each just100 nanometers wide – which break up into smaller particles whenthey reach the tumor sight. The drug-loaded nanoparticles aretransported to the tumor through blood vessels, at which point theacidic environment around the cancer cells causes them to break up,discharging 5-nanometer-wide particles to the disease site.
These even smaller particles, which theresearchers call "bomblets" then move inside the tumor cells, atwhich point the platinum-based cisplatin drug is activated, damaging DNA tokill off the cells.
The use of cisplatin isn't new, butadministering the drug without the use of the nanoparticles – knownas free cisplatin – has toxic effects across the body. However,when the pH-sensitive particles are used get the medication totumors, the negative effects appear to be significantly lowered.
Testing the method on laboratory micewith human pancreatic tumors, the researchers found that the samedose of cisplatin delivered via the nanoparticles resulted in a seventimes higher concentration of the drug in tumor tissue than with freeclisplatin delivery. The fact that so much more of the drug made itsway into the tumors with the new method means that less of thesubstance was dispersed into other areas of the body, lowering thetoxic side effects.
Of course, with much more of the drugpresent in tumors, its effectiveness at tackling the disease is alsoimproved. In lung cancer models, the researchers found free cisplatinprovided 10 percent growth inhibition, while the same dose deliveredvia nanoparticles yielded 95 percent growth inhibition. The method wasalso tested with invasive metastistic breast cancer in mice, where itextended the amount of time that the animals survived by almost 50percent.
"The negative side effects ofcisplain are a long-standing limitation for conventionalchemotherapy," said lead paper author Jinzhi Du. "In our study,the delivery system was able to improve tumor penetration to reachmore cancer cells, as well as release the drugs specifically insidecancer cells through their size-transition property."
Full details of the new drug deliverymethod are available online in the Proceedings of the National Academy of Sciences.
Source: Emory University