"Based on the promising results of our theoretical calculations, we believe that the use of AuNPs represents enormous possibilities for improving radiation therapy," assistant professor Ross Berbeco from Harvard's Department of Radiation Oncology told nanotechweb.org's sister website, medicalphysicsweb. "Our goal is to develop an agent that can be used clinically in combination with conventional radiotherapy beams to provide an additional boost of destructive energy to an important piece of the tumour architecture."

Targeted therapy

One as yet unanswered question in radiotherapy is the role that tumour vasculature, and in particular endothelial cells, plays in the success of therapy. Over the last few years, nanoparticles have gained much interest as either platforms to carry tumouricidal drugs or as agents themselves for enhancing therapy. In this study, the researchers exploit the fact that nanoparticles preferentially accumulate in the tumour vasculature and are essentially dormant until they are bombarded by an X-ray source.

In the presence of low-energy X-rays of around 100–keV, the AuNPs emit photoelectrons that travel a very short distance before depositing their energy in the nearest endothelial cell. "Others have dismissed the dose enhancement that could be initiated by a 6–MV linac photon energy spectrum," commented Berbeco. "We realised that the dose enhancement is sizable at a short distance from the nanoparticles and that the local radiation boost is actually quite substantial. Our method is a doubly targeted therapy. The nanoparticles target the tumour vasculature while the megavoltage radiation targets the tumour."

Modelling the interactions

Berbeco and colleagues modelled a tumour vascular endothelial cell as a thin slab measuring 2 x 10 x 10 µm, where a circle of seven cells forms an idealised segment surrounding a blood vessel. Nanoparticles with a diameter of 100 nm are then modelled in a random distribution along the interior endothelial cell wall.

The team presents its results using a value called the "endothelial dose enhancement factor" (EDEF) – a ratio of the dose absorbed by the endothelial cells in the presence of AuNPs divided by the absorbed dose without AuNPs. The overall EDEF depends on the local concentration of nanoparticles.

According to Berbeco, the majority of the dose enhancement originates from the low-energy (100 keV) portion of the linac X-ray spectrum. Taking into account the probability of a 100 keV photon generating a photoelectron in a 100 nm AuNP, the extra dose deposited in an adjacent endothelial cell is approximately 3.7 mGy per photoelectron per nanoparticle. At a depth of 20 cm, this equates to an EDEF of 1.7 (a 70% dose increase) for a local intravascular AuNP concentration of 30 mg/g.

"We were surprised to find that so much endothelial dose enhancement was possible for a conventional 6 MV linac beam," commented Berbeco. "This opens up some exciting possibilities for new therapies."

Putting theory into practice

The team is now setting up in vitro and in vivo studies to test its hypothesis and quantify the extent to which gold nanoparticles can cause tumour endothelial cell damage. "In vivo studies will be needed to quantify the amount of gold that can be safely sequestered in the tumour vasculature," said Berbeco. "It is also worth noting that for a flattening filter free beam, the proportion of low-energy photons will be substantially increased which should lead to a further enhancement of the dose."