Chemotherapy drugs are effective at killing cancer cells – but unfortunately, they're also pretty good at killing healthy cells. Making these drugs more selective for tumors is a key area of research, and now a team at ETH Zurich has found a way to keep a common treatment – platinum nanoparticles – on target.

To make platinum toxic to living cells, it first needs to be oxidized, creating a form known as platinum(II). But doing this too early in the process is what leads to the collateral damage of healthy cells. Past attempts to skirt this problem have involved wrapping the drug payload in a larger particle that protects it until it reaches the tumor, or creating drugs that also treat the side effects, such as kidney damage, at the same time.

For the new work, the ETH Zurich team started with non-oxidized platinum nanoparticles, 2.5 nanometers wide. The researchers then scanned a library of peptides until they found one that could keep the platinum particles stable for years at a time. The idea was to keep them non-oxidized until they enter the cancer cells, at which point the highly oxidative environment in the tumors converts the harmless platinum(0) into toxic platinum(II).

The team tested the new nanoparticles on samples of 10 different types of human cells, both cancerous and healthy. Sure enough, the drugs were found to only become toxic in liver cancer cells, and not healthy ones. The nanoparticles proved to be just as effective against tumors as Sorafenib, the most common liver cancer drug in use today, but were far more targeted to tumors. They performed even better when compared to another common chemo drug, Cisplatin.

The researchers say that the new technique could eventually be used to make treatments that have fewer side effects without skimping on the effectiveness against tumors. That said, the platinum nanoparticles seemed to perform particularly well against liver cancer, but not quite as much against other forms of the disease, such as colorectal cancers.

"We are still a very long and uncertain way away from a new drug, but the research introduced a new approach to improve the selectivity of drugs for certain types of cancer – by using a selective activation process specific to a given cell type," says Helma Wennemers, lead researcher on the study.

The research was published in the journal Angewandte Chemie.

Source: ETH Zurich

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