Platinum Nanoparticles Offer ‘Selective Treatment’ of Liver Cancer Cells


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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

Read more at: https://phys.org/news/2019-02-platinum-nanoparticles-treatment-liver-cancer.html#jCp

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Nano-Antioxidant With Longer Shelf Life For Better Anti-Aging Cremes and Food


QDOTS imagesCAKXSY1K 8Scientists from ETH Zurich have developed a nanomaterial  that protects other molecules from oxidation. Unlike many such active  substances in the past, the ETH-Zurich researchers’ antioxidant has a  long shelf life, which makes it just the ticket for industrial  applications.

There is a lot of talk about antioxidants. These chemical compounds are found in many fruit and vegetable varieties, coffee, tea and red wine, and are generally regarded as healthy. After all, antioxidants protect the body’s own proteins and the genetic substance from oxidation. Antioxidants are also used in industry, including as food additives to preserve items for longer or exploit the health aspect as a selling point. They are in food packaging or car tires to prevent the synthetic material or rubber from becoming brittle. And in the cosmetics industry creams with antioxidants are advertised as anti-aging products.

The problem in using antioxidants, however, is that many of these molecules are not actually very stable in themselves. For instance, they are oxidized in the presence oxygen and gradually lose their antioxidant effect. Researchers under Yiannis Deligiannakis, a visiting professor at the Institute of Process Engineering, have now developed a special nanoantioxidant that is considerably more stable than its conventional counterparts, which means it can be stored more easily and is effective in smaller amounts.

Nanoparticles prevent interaction

The ETH-Zurich scientists’ nanoantioxidant is composed of a silicon dioxide nanoparticle and the naturally occurring antioxidant gallic acid, whereby the two parts are firmly bonded. “Gallic acid is one of the molecules with the best antioxidant activity,” explains Georgios Sotiriou, who was involved in the project as a postdoc at the Institute of Process Engineering before moving to Harvard University. However, as with other antioxidants, gallic acid molecules soon lose their effect, especially since they like to latch onto other gallic acid molecules and thus deactivate each other. By combining them with the silicon dioxide, however, the researchers were able to suppress this process. After all, the large nanoparticles compared to the gallic acid molecules prevent the latter from interacting with each other: for reasons of space, they are no more capable of doing so than passengers in two hot-air balloons are of reaching out and touching each other.

ETH Zurich's researchers coupled gallic acid with silicon dioxide nanoparticles to stabilize the antioxidant.
(Photo : Edisa Balje / ETH Zurich) ETH Zurich’s researchers coupled gallic acid with silicon dioxide nanoparticles to stabilize the antioxidant.

“Our nanoantioxidant has the same outstanding effect as gallic acid, but can be sold as a product with a long shelf life for industry,” says Deligiannakis. Moreover, the nanoantioxidant is temperature-resistant and could thus protect food that is pasteurised or polymers that are produced at high temperatures. Conventional antioxidants become inactive at these temperatures.

A safe combination

The researchers have now patented their new product and are currently in talks with industrial partners with regard to licensing. The scientists do not expect any major hurdles as far as the safety of the molecule is concerned: both gallic acid and the silicon dioxide nanoparticles are deemed harmless, have been approved by the authorities – including for use in food – and are in active usage. The scientists thus expect tests to confirm that the combination molecule is also safe for cosmetics and food. — Source: Fabio Bergamin, ©2013 ETH Zurich (Federal Institute of Technology Switzerland), posted by Mark Hoffman 

Reference:

Deligiannakis Y, Sotiriou GA, Pratsinis SE: Antioxidant and Antiradical SiO2 Nanoparticles Covalently Functionalized with Gallic Acid. ACS Applied Materials & Interfaces, 2012, 4, 6609-6617, doi: 10.1021/am301751s