Schematic representing the keratin-templated formation of the gold nanoclusters, modification with silver and gadolinium, loading with drug and imaging by near-infrared light or magnetic resonanceKeratin, the main protein in hair, is surprisingly useful for assembling gold atoms into fluorescent nanoclusters that may help deliver drugs to their targets and image diseased tissues for diagnosis.
Guang Yang at Donghua University in Shanghai and her team report on the self-assembly of keratin-templated gold nanoclusters in the journal Acta Biomaterialia. The nanoclusters were also modified to develop enhanced fluorescence and stability.
To form a nanocluster, gold atoms must be induced to assemble into collections only several nanometres wide. Many research teams have used various proteins as effective templates encouraging cluster formation, but researchers continue to seek more effective protein templates to make clusters with improved properties.
The protein keratin has a unique structure, due to the presence of many chemical bonds between sulfur atoms (disulfide bonds) on neighbouring strands of the protein molecular chains. These bonds help give keratin the strength to build hair, nails, feathers and other strong tissues in animals.
“This unique structure inspired us to explore ways to synthesize an assembly of gold nanoclusters,” says Yang.
The researchers extracted keratin from feathers and mixed it with a solution of a gold-containing compound. After a few simple chemical treatments, the mixture yielded gold nanoclusters combined with keratin.
The nanoclusters fluoresced brightly when stimulated with near-infrared radiation. This has the range wavelengths that can penetrate into the body, a region known as the therapeutic window.
Adding silver ions produced modified nanoclusters with more than six times greater fluorescence. The researchers made a third type of nanocluster by adding ions of the metal gadolinium. This form proved to be particularly suitable for detection by magnetic resonance imaging.
Studies in mice indicated that the nanoclusters showed good biocompatibility.
Fluorescent nanoparticles, including metallic nanoclusters, are being applied widely in biomedical imaging applications. They can be used to reveal and monitor the cells and tissues that they are directly introduced to, or which they can be made to bind with and enter. Coating nanoparticles with antibodies, for example, can allow them to selectively bind to and enter chosen cells and tissues, including cancers.
Yang expects the excellent fluorescent intensity, stability and biocompatibility of the gold nanoclusters could assist in many such imaging applications.
To explore potential uses in drug delivery, the researchers loaded the gadolinium-modified nanoclusters with the anticancer drug doxorubicin. They found that the drug was effectively released in chemical conditions mimicking those of a tumour. This effect, which they attributed to the response of the disulfide bonds in the keratin, suggests opportunities for selective drug delivery into tumours.
Tests on live mice confirmed the anti-cancer potential of the gadolinium-modified nanoclusters. Fourteen days after commencing treatment, tumours growing in treated mice were less than half the volume of those in untreated controls.
“Keratin has not received much attention for a long time,” Yang says, pointing out that she believes this protein may offer further opportunities for her group and others to explore.
Article details:
Yang, G. et al.: “The assembly of protein-templated gold nanoclusters for enhanced fluorescence emission and multifunctional applications,” Acta Biomaterialia (2020)
Acta Biomaterialia is part of the family of Acta Materialia Inc journals, which also includes Acta Materialia, Scripta Materialia and the newly launched Materialia.