Community Research and Development Information Service - CORDIS

Towards high-throughput drug screening

Drug discovery is a laborious and expensive process that involves many time-consuming steps. The great medical need for effective drugs, however, necessitates novel methodology.
Towards high-throughput drug screening
Traditional screening methods hamper the pace and success rate of drug development. This leads to ineffective treatment, complications from improper dosages and a greater healthcare burden. According to the US Food and Drug Administration, only ~8 % of the drug candidates that enter clinical trials are eventually approved, requiring rapid and effective drug screening.

To expedite drug candidate screening, the EU-funded FUNSTAR CAPSULE (Functional nanostar encapsulated nanocapsule for cell-based high-throughput drug screening) project proposed a novel methodology based on colorimetric readout. This method relies on the aggregation state of gold nanoparticles (NPs) and offers rapid screening of drugs for cancer, epilepsy, glaucoma, AIDS and inhibitors of sphingomyelinase (SMase), an enzyme associated with cardiovascular and Niemann-Pick diseases.

For screening drug candidates, a smart strategy was developed for the first time using synthetic probes and an enzyme in a colorimetric assay. Researchers initially synthesised appropriate ligands with target binding ability and coupled them to chromophore tags. The binding kinetics and thermodynamics of these ligands were characterised by surface plasmon resonance, isothermal titration calorimetry, and UV-Vis spectroscopy. Effective drugs with higher binding affinity towards the target protein produced colour change from red to blue. Overall, the method proved to be very robust with drug inhibitory concentrations matching the binding affinities.

A modified version of this method was implemented towards the screening of SMase inhibitors. Researchers developed liposome vesicles containing the natural substrate of the enzyme, which was released upon vesicle disruption, causing gold NPs aggregation and hence colour change.

The NP-based method developed by FUNSTAR CAPSULE offers an efficient and rapid platform for screening drug candidates using colour responses. The ease, sensitivity and time-effectiveness of the approach could significantly expedite drug discovery.

Related information

Subjects

Life Sciences

Keywords

Drug discovery, nanoparticle, cancer, inhibitor, sphingomyelinase, colourimetric
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