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NUS researchers discover new and less toxic anti-cancer drug

Researchers from The National University of Singapore (NUS) have created a new anti-cancer drug which is less harmful to the kidneys.

This novel medicine functions such that it is directly delivered to the mitochondria of cancer cells. Mitochondria is the power generator of cells.

Two active molecules, an anti-cancer drug and a sensitizer, are released at once when the drug reaches the tumour.

Thee molecules will fight the mitochondria of the cancer cells and kill the cells. This ensures that the drug is transferred to its destination, reducing its exposure to other tissues in the body.

Side-effects are reduced and there is a lower possibility of patients developing resistance to the drug with this targeted approach. This is unlike current anti-cancer drugs such as Cisplatin.

Cisplatin is an anti-cancer drug in 1965. Back in the days, it was regarded as a revolutionary form of medicine for treating cancer and increasing cure rates.

Fast-forward to today, Cisplatin and the newer medicine such as the platinum-based anti-cancer drugs are still used in about 40 per cent of all chemotherapy treatments. However, these drugs have dangerous side effects. Some of these include severe kidney dysfunction in patients which may require some patients to undergo dialysis treatment.

Cisplatin is often used as a gold standard and a benchmark for comparing new medicines to as shared by Associate Professor Ang Wee Han from NUS Chemistry.

“Cisplatin is known to kill cancer cells by damaging DNA. But cancer cells are smart, and they have ways to repair this damage and become resistant to the drug treatment. Hence, we need good alternatives that can address drug resistance and the associated side effects,” he said.

Professor Ang and Associate Professor Giorgia Pastorin from NUS Pharmacy had together researched into creating anti-cancer drug which will provide better solutions and be used in place of Cisplatin as a better alternative.

The research was conducted together with Professor Dan Gibson from The Hebrew University of Jerusalem.

Experiments conducted with the new drug found that the tumour from a colon cancer had shrunk such that the tumour became impalpable.

The direct delivery of the drug to the tumour had allowed for this.

This was made possible with the team adding a mitochondria-targeting ligand to the original cisplatin scaffold. The added ligand served as a strong positive charge that strongly corresponded the negative charge of the mitochondrial membrane.

The researchers then observed how the drug was released into the blood and devised a way to contain the drug’s formulation within tiny drug carriers known as liposomal nanovesicles.

The nature of tumours is such that they grow fast, blood vessels, as a result, are unable to properly develop and become leaky.

With this new feature to the drug, permeation of the drug carriers from blood vessels to the tumour microenvironment is achieved and will stay within the tumour, while attacking the cancer cells.

As mentioned earlier, the new drug brought no side effects to the body.

“No sign of kidney inflammation was detected, unlike the use of conventional cisplatin. These results indicate that our invention is a viable alternative to cisplatin,” said Dr Maria Babak, the first author of the study.

Associate Professor Pastorin said that the team wants to push the boundaries and further enhance the drug such that it will allow for total tumour remission and overcome the challenge of drug resistance.

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