Nanostructures can be used to deliver drugs inside tumour cells. However, how efficient they are at this task depends on a variety of factors, and one of the most critical of these is the shape of the structure. It is therefore important to understand which shapes are best, but until now such studies have been difficult because it is difficult to track the movement of nanostructures in vivo.

A team of researchers led by Younan Xia from Georgia Tech and Yongjian Liu of Washington University has now successfully prepared gold nanostructures containing radioactive Au-198 in their crystal lattices. The nanostructures were made in four distinct shapes (disks, rods, spheres and cubic cages) but were all roughly the same size (between 50 and 100 nm across). By measuring the gamma radiation as the Au-198 decays, the researchers were able to follow how the nanostructures distributed themselves in mice with tumours.

Better strategies for cancer imaging and therapy

“In our experiments, we compared the intratumoural distribution of the four types of nanostructure in a mouse breast-cancer xenograft and observed that the different shapes penetrated into the tumour site at different rates and also distributed themselves differently there,” explains Xia. “Our findings should help us develop better strategies for cancer imaging and therapy.”

The gold nanodisks made by the researchers are 2D circles 7 nm thick and 100 nm in diameter. The nanorods are 1D structures that are 10 nm wide and 50 nm across. The nanospheres are round in shape with a diameter of around 50 nm. Finally, the nanocages are cubic hollow nanostructures with pores in their walls. Their edge length is around 50 nm and their walls are about 5 nm thick.

Shape matters

The researchers also found that the nanorods did not accumulate in the tumour sites as readily as the other shapes. However, because the nanorods were less than 50 nm in diameter, they were able to leak out through the pores in the mircovasculature of a tumour and penetrate into its core. In contrast, the nanospheres and nanodisks were only able to reside on the surface of the tumours, said Xia. “Interestingly, we found that the cubic nanocages accumulated inside the core of the tumour too – a phenomenon that we believe comes about thanks to their hollow structure and relatively low density,” he told

“Our study shows that the shape of Au nanostructures is important for how these particles enter and distribute themselves in tumours,” he added.

The Georgia Tech-Washington team says that it will now focus on reducing the size of the nanostructures they studied so that they can stay in the bloodstream for longer periods and better penetrate cancer cells at the same time. “We also plan to test these radioactive nanostructures on other tumour models, such as orthotopic mouse breast-cancer cells,” he said. “We will further functionalize the surface of these structures with targeting ligands so that tumour cells take them up more readily.”

The current work is detailed in ACS Nano DOI: 10.1021/nn406258m.