A bright spark for brain imaging and therapy

Most drugs cannot cross the blood–brain barrier without disruption

November 25, 2017 08:06 pm | Updated 08:08 pm IST

 “Glutathione also facilitates uptake of amino acids into the brain,” explains R.S. Jayasree (second from right)

“Glutathione also facilitates uptake of amino acids into the brain,” explains R.S. Jayasree (second from right)

A new nanocluster that is able to cross the blood–brain barrier has been developed by scientists at Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), Thiruvanathapuram. The fluorescent gold nanocluster of size 1.7 nanometre can be used both as a carrier of drugs to the brain and for imaging the brain for tumours and other disorders. The results were recently published in the Journal of Materials Chemistry B.

The blood–brain barrier is a highly selective semipermeable membrane that separates the circulating blood from the extracellular fluid in the central nervous system (brain). Most of the drugs cannot cross this barrier without disrupting it, and this is a major challenge in treating brain disorders. The nanocluster was able to cross the barrier without causing disruptions.

Facilitator

To enable the nanocluster to cross the barrier, the researchers coated the gold nanoparticles with glutathione. “Glutathione is a tripeptide and is found virtually in every cell of the human body and so has no safety concerns. The glutathione also facilitates the uptake of amino acids into the brain,” explains Dr R.S. Jayasree, scientist at the institute and the corresponding author of the paper. “For targeted and enhanced entry of the gold cluster, a brain targeting amino acid (L-dopa) was added. In mice models, the nanocluster injected intravenously reached the brain almost completely in just few minutes.”

“We can tune the fluorescence emission to any wavelength by controlling the conditions like pH, temperature etc. during the synthesis of the cluster. We chose near-infrared wavelength, as otherwise, emissions from our body will hinder the imaging of the tumour,” she adds.

For drug delivery studies, a model drug pilocarpine (a seizure-inducing agent) added to the nanoparticle was injected into the mice. The animals showed the preliminary neurological symptoms, but never had seizures, indicating that the gold nanoclusters released the drug slowly.

The new nanocluster can be used for the early stage diagnosis and treatment of neurological diseases when the barrier is not disrupted or loosened, the authors claim.

More studies are required before going for human clinical trials since the blood–brain barrier varies from species to species.

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