Nanoparticle "cluster bombs" could provide less toxic chemotherapy

The treatment ensures that more of the drug makes it into the tumor tissue, limiting toxic side effects in other parts of the body(Credit: Emory University)

Doctors have been using the chemotherapy drug cisplatin for decades, but significant toxic side effects – which can affect everything from the kidneys to the inner 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 signs of being significantly less toxic to the patient.

The ongoing battle against cancer presents a monumental challenge for medical researchers, but potentially significant breakthroughs are being made on a regular basis. Just this week, scientists at the Brigham and Women's Hospital announced that they had successfully tested nanoparticles engineered to glow in the presence of dying cells, providing a real time indication of treatment effectiveness.

Now, a collaborative team of researchers from the University of Science and Technology of China, Georgia Tech and Emory University, has also turned to nanoparticles, but with a very different goal in mind – to improve the delivery of drugs to tumors.

Designed to deliver the chemotherapy drug cisplatin, the system makes use of tiny nanoparticles – each just 100 nanometers wide – which break up into smaller particles when they reach the tumor sight. The drug-loaded nanoparticles are transported to the tumor through blood vessels, at which point the acidic environment around the cancer cells causes them to break up, discharging 5-nanometer-wide particles to the disease site.

These even smaller particles, which the researchers call "bomblets" then move inside the tumor cells, at which point the platinum-based cisplatin drug is activated, damaging DNA to kill off the cells.

The use of cisplatin isn't new, but administering the drug without the use of the nanoparticles – known as free cisplatin – has toxic effects across the body. However, when the pH-sensitive particles are used get the medication to tumors, the negative effects appear to be significantly lowered.

Testing the method on laboratory mice with human pancreatic tumors, the researchers found that the same dose of cisplatin delivered via the nanoparticles resulted in a seven times higher concentration of the drug in tumor tissue than with free clisplatin delivery. The fact that so much more of the drug made its way into the tumors with the new method means that less of the substance was dispersed into other areas of the body, lowering the toxic side effects.

Of course, with much more of the drug present in tumors, its effectiveness at tackling the disease is also improved. In lung cancer models, the researchers found free cisplatin provided 10 percent growth inhibition, while the same dose delivered via nanoparticles yielded 95 percent growth inhibition. The method was also tested with invasive metastistic breast cancer in mice, where it extended the amount of time that the animals survived by almost 50 percent.

"The negative side effects of cisplain are a long-standing limitation for conventional chemotherapy," said lead paper author Jinzhi Du. "In our study, the delivery system was able to improve tumor penetration to reach more cancer cells, as well as release the drugs specifically inside cancer cells through their size-transition property."

Full details of the new drug delivery method are available online in the Proceedings of the National Academy of Sciences.

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