Elevated enzyme for cancer diagnosis:

Elevated enzyme for cancer diagnosis:

Context

• The application of the elevated enzyme technique may be used during surgery to know tumour spread.
• Researchers have utilised the overexpression of biotin receptors on cancer cells and enhanced production of thioredoxin reductase (TrxR) enzyme in cancer cells for cancer diagnosis.
• Breast and cervical cancer cell line studies shows encouraging results.

More about the research and findings

• The researchers developed a hybrid assembly by binding naphthalimide moiety to carbon dots using disulphide covalent bond.
• Naphthalimide analogues are used as anticancer agents.
• In the presence of normal amount of TrxR enzyme seen inside normal cells, the carbon dots behave as an energy donor and the naphthalimide moiety as an acceptor, thus establishing fluorescence resonance energy transfer (FRET).
• There is a typical yellow emission when irradiated with visible light.
• But in the presence of elevated levels of TrxR enzyme, which is seen in cancer cells, the disulphide covalent bond gets disrupted freeing the naphthalimide moiety from the surface of carbon dots.
• As a result, the FRET gets disrupted and there is blue emission when the cells are irradiated with visible light.
• In normal cells, the amount of TrxR enzyme is very little and hence the FRET mechanism is not eliminated, resulting in yellow emission.

What is fluorescence resonance energy transfer (FRET)?

• Fluorescence Resonance Energy Transfer (FRET) is a physical phenomenon whereby energy created by fluorescence excitation of one molecule is transferred to an adjacent molecule.
• Basically, FRET is a special technique to gauge the distance between two chromophores, called a donor-acceptor pair.
• If the two molecules are fluorophores, excitation of the first molecule results in fluorescence emission of the second molecule.

Distinguishing cancer cells using colour of the emission

• We can distinguish cancer cells from normal cells by the colour of the emission.
• The presence of yellow emission indicates normal cells while blue indicates cancer cells.
• Note: i) Unlike normal cells, cancer cells have large number of biotin receptors. Since biotin is present on the surface of carbon dots, the hybrid assembly is absorbed in large numbers by cancer cells. ii) When the bond is intact the emission comes from the naphthalimide moiety, and when the bond is broken, the emission comes from the carbon dots
• Within 45 minutes of treatment, we could see the change in emission from yellow to blue.
• Since visible light cannot penetrate human tissue, the potential application of this technique may be during surgery to know tumour spread.

Therapeutic Use of this technique

• The naphthalimide used here can function as a cancer therapeutic.
• The nanosensor was found to reduce the viability of cancer cells up to 70%.
• The naphthalimide that gets released when the disulfide bond is broken is responsible for the destruction of cancer cells.
• Higher concentration of naphthalimide is used to kill 70% of cancer cells. Usually, much lower concentration of drug is used for therapeutic purposes.

Way Forward

• Since naphthalimide is expensive, the researchers are trying to develop a cheaper substitute.
• The new hybrid material would be tested on more cancer cell lines before testing it on animal models.
• The focus is on using the assembly for diagnostics. If it offers therapeutic benefits then it will be an added advantage.

Note: Inspirational Quotes by APJ Abdul Kalam on his birthday anniversary