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Researchers at the Federal Institute of Technology in Zurich have recently demonstrated that platinum nanoparticles can be used to kill liver cancer cells with a higher selectivity than existing anticancer drugs.
In recent years, the number of targeted anticancer drugs has continued to increase. However, conventional chemotherapeutic agents still play an important role in cancer treatment. These include platinum -based cytotoxic agents that attack and kill cancer cells . But these drugs can also damage healthy tissue and cause serious side effects. Researchers at the Federal Institute of Technology in Zurich have now identified a way to use these drugs for more selective cancer treatment.
When oxidized to platinum (II), platinum can be cytotoxic and is present in this form in conventional platinum-based chemotherapeutic agents. However, unoxidized platinum (0) is much less toxic to cells. Based on this knowledge, a team led by Helma Wennemers, a professor of organic chemistry labs, and her team's postdoctoral Michal Shoshan, sought a way to introduce platinum (0) into target cells before they began to be oxidized to platinum (II). To this end, they used non-oxidized platinum nanoparticles, which must first be stabilized with peptides. They screened libraries containing thousands of peptides to identify peptides suitable for the production of stable platinum nanoparticles (2.5 nm in diameter) for many years.
Oxidation in cells
Tests with cancer cell cultures showed that platinum (0) nanoparticles penetrated into the cells. Once in the specific environment of liver cancer cells, they are oxidized, triggering the cytotoxic effects of platinum (II).
Studies on ten different types of human cells have also shown that the toxicity of peptide-coated nanoparticles is highly selective for liver cancer cells. They have the same toxic effects as sorafenib, which is currently the most commonly used drug for the treatment of primary liver tumors. However, nanoparticles are more selective than sorafenib and are significantly more selective than the well-known chemotherapeutic cisplatin. It is therefore conceivable that the nanoparticles have fewer side effects than conventional drugs.
In collaboration with ETH Professor Detlef Günther and his team, Wennemers and her team used specific mass spectrometry to determine the amount of platinum in cells and their nuclei. They concluded that the platinum content in the nucleus of liver cancer cells is significantly higher than that in, for example, colorectal cancer cells . The authors believe that platinum (II) ions - platinum nanoparticles produced by oxidation - in liver cancer cells - enter the nucleus and have the toxicity to release them.
“We are still a long-term and uncertain way to stay away from new drugs, but the study introduces a new way to increase the selectivity of drugs for certain types of cancer – through the selective activation process using specific cell types,” Wennemers Say. Future research will expand the chemistry of nanoparticles to better control their biological effects.
Further exploration: gold nanoparticles transfer platinum warheads to tumors
For more information: Michal S. Shoshan et al. Peptide-coated platinum nanoparticles with selective toxicity to liver cancer cells, Angewandte Chemie International Edition (2018). DOI: 10.1002 / anie.201813149
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