Platinum Nanoparticles Offer ‘Selective Treatment’ of Liver Cancer Cells

Non-oxidised platinum nanoparticles have virtually no toxic effect on normal cells (bottom left). Once inside liver cancer cells (top right), the platinum is oxidised, releasing its toxic effect. Credit: ETH Zurich / Helma Wennemers

Researchers at ETH Zurich recently demonstrated that platinum nanoparticles can be used to kill liver cancer cells with greater selectivity than existing cancer drugs.

In recent years, the number of targeted  has continued to rise. However, conventional chemotherapeutic agents still play an important role in cancer treatment. These include -based  that attack and kill . But these agents also damage healthy tissue and cause severe side effects. Researchers at ETH Zurich have now identified an approach that allows for a more selective cancer treatment with drugs of this kind.

Platinum can be cytotoxic when oxidised to platinum(II) and occurs in this form in conventional platinum-based chemotherapeutics. Non-oxidised platinum(0), however, is far less toxic to cells. Based on this knowledge, a team led by Helma Wennemers, Professor at the Laboratory of Organic Chemistry, and Michal Shoshan, a postdoc in her group, looked for a way to introduce platinum(0) into the , and only then for it to be oxidised to platinum(II). To this end, they used non-oxidised platinum nanoparticles, which first had to be stabilized with a peptide. They screened a library containing thousands of peptides to identify a peptide suitable for producing platinum nanoparticles (2.5 nanometres in diameter) that are stable for years.

Oxidised inside the cell

Tests with cancer cell cultures revealed that the platinum(0) nanoparticles penetrate into cells. Once inside the specific environment of liver cancer cells, they become oxidised, triggering the cytotoxic effect of platinum(II).

Studies with ten different types of human cells also showed that the toxicity of the peptide-coated nanoparticles was highly selective to liver cancer cells. They have the same toxic effect as Sorafenib, the most common drug used to treat primary liver tumours today. However, the nanoparticles are more selective than Sorafenib and significantly more so than the well-known chemotherapeutic Cisplatin. It is therefore conceivable that the nanoparticles will have fewer side effects than conventional medication.

Joining forces with ETH Professor Detlef Günther and his research group, Wennemers and her team were able to determine the platinum content inside the cells and their nuclei using special mass spectrometry. They concluded that the platinum content in the nuclei of liver cancer cells was significantly higher than, for instance, in colorectal cancer . The authors believe that the platinum(II) ions – produced by oxidation of the  in the  – enter the nucleus, and there release their toxicity.

“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  – by using a selective activation process specific to a given cell type,” Wennemers says. Future research will expand the chemical properties of the nanoparticles to allow for greater control over their biological effects.

 Explore further: Gold Nanoparticles Delivery Platinum Warheads to Tumors

More information: Michal S. Shoshan et al. Peptide-Coated Platinum Nanoparticles with Selective Toxicity against Liver Cancer Cells, Angewandte Chemie International Edition (2018). DOI: 10.1002/anie.201813149

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Nanopolymers Open New Way to Detect Cancerous Tumors

201306047919620The drug which was synthesized in association with Control Laboratory of Food and Drug Department of Iran’s Ministry of Health, Hygiene, and Medical Education can be used in MRI as the contrast agents in addition to curing cancerous tumors.
The aim of this study was to evaluate the contrast optimization of silicon-based gadolinium oxide nanoparticles with nanocomposite coating, and to compare gadolinium nanoparticle with the common contrast agent in magnetic resonance imaging (Magnevist). In this study, the new emulsion made of gadolinium oxide nanoparticle and POSS-PCU nanocomposite was investigated. In comparison with Magnevist, gadolinium oxide nanoparticles can increase the signal of MRI by reducing relaxation time or by increasing the rate of relaxation.

They can also create high contrast optimization in MRI as positive contrast in comparison with iron oxide nanoparticles (negative contrast agent).
In line with targeting methods and through connecting to biocompatible materials, the new medicine has obtained other useful results in drug delivery in order to detect lymphatic glands of breast cancer and hepatic tumors.
Since the non-nanoic sample of this drug has acquired the confirmation of US Foodstuff and Medications Standard Organization, it has FDA certificate. The drug has passed the laboratorial and animal tests, and it is going to be tested on humans too.
Results of the research have been published in December 2010 in Biological Trace Element Research, vol. 137, issue 3. For more information about the details of the research, study the full article on pages 324-334 on the same journal.


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