Making cellular probes more effective

  • By Kollegala Sharma (Twitter handle: @kollegala)

Mysuru, August 8   : Scientists at Indian Institute of Science, Bengaluru have found a way to enhance uptake of fluorescent probes into cells.

They have found that by replacing hydrogen atoms at crucial places of napthalimide with iodine or bromide atoms makes it easier to break into cells. Napthalimide molecule shines under ultraviolet light by itself or when combined with any other molecule, and hence is used as fluorescent probe. 

Fluorescent probesare used to detect molecules, monitor cellular activity and deliver drugs inside cells. Fluorescent probes based on naphthalimide are especially popular as they can easily be made in large quantities and their fluorescence can be tweaked by changing their constituent atoms. Besides they are not harmful like radioactive ones. However, they are usually absorbed by cells only in small quantities, which hampers their effectiveness.

Researchers led by Prof GovindaswamyMugeshfound that simply replacing two hydrogen atoms with iodine in their structure dramatically increased the amount entering into mammalian cells. Almost 98% of all probescan enter the cell if iodine or bromine atoms are tagged to it.

The team designed fifteen naphthalimide-based probes and tested how they would fare, if some of the hydrogen atoms in their structure are replaced with chlorine, bromine or iodine. The uptake increased upto 15% with chlorine and 22% with bromine atoms, but went up to 98% whentwo iodine atomswere added.

Further investigation revealed that the two iodine atoms formed strong bonds with a transporter protein called MCT8 which then ferried the molecule in to the cells. MCT8 is known to transport hormones such as thyroxine, into the cells. For example, thyroxine (T4), the hormone secreted by the thyroid gland, needs to be transportedfrom the blood to inside the cell where it gets converted to T3, its functional form.  That adding iodine increases cellular uptake suggests that biological compounds containing iodine probably use a similar transporter protein and mechanism to enter into cells.

Such probes containing iodine could help analyze membrane activity and track thyroxine. “There is no probe to understand how much T4 is transported inside the cells. Generally, it is measured by using radioactive iodine.  But our method is a simple fluorescent method, which does not use any radioactive compounds, to find out whether MCT8 is functioning properly or not, and if hormone uptake is affected or not”, researchers said.

The research team includedHarinarayanaUngati, and VijayakumarGovindaraj, beisdedMugesh. The research results have been published recently in journal AngwadteChemie. The study was funded by the Science and Engineering Research Board (SERB). (India Science Wire)

 

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