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NUS Chemists Develop Novel Ratiometric Fluorescent Probe

NUS chemists have developed a novel ratiometric fluorescent probe, known as RDC1, for studying cellular activity of the clinically important anticancer drug cisplatin for next generation drug development.

RDC1 is a useful tool which can empower researchers to better understand the way platinum(IV) prodrug complexes are processed at the cellular level.

RDC1 is designed to differentiate cisplatin from its structurally-similar platinum (IV) analogues for fluorescence imaging at the cellular level.

As a ratiometric probe, RDC1 changes emissions/colours between 2 different emission/colour channels as more cisplatin is detected.

This is a more accurate way of quantifying minute amounts of analyte compared to single emission/colour intensity-based probes because detectors perceive emission/colour changes more acutely than intensity changes.

Cisplatin has become one of the most important chemotherapeutic agents in clinical use.

It is widely used to treat a variety of malignancies such as testicular, ovarian and colorectal cancers. And is also a part of a class of platinum (II) anticancer agents.

Platinum(IV) scaffolds are used in clinical trials that are involved in the investigation of the next generation of platinum anticancer agents (prodrug complexes).

The platinum anticancer drugs are biologically inactive compounds and they can be metabolised in cancer cells to produce bioactive platinum (II) agents.

The drawbacks of traditional platinum (II) agents such as high toxicity and other severe side effects can be overcome with these new drug candidates.

However, pharmacological effect at the cellular level that is produced by their biochemical interaction with cancer cells is not clear.

RDC1 is able to detect and measure cisplatin effectively in a complex cellular environment containing an assortment of many other metal ions and biomolecules.

The usual method of quantifying cisplatin is to measure the platinum content in cancer cells through elemental analysis.

But, the method is destructive and does not distinguish one form of platinum from another.

The visualisation of the conversion of platinum (IV) prodrug complexes within cancer cells is found and identified that they are activated by a chemical reduction process to produce cisplatin.

Scientists also found that glutathione, a cellular antioxidant found in our bodies, is not the dominant biomolecule affecting this chemical reduction process, which is different to many research reports.

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