Have scientists found the next golden opportunity in the fight against prostate cancer?

Scientists investigate whether gold nanoparticle-enhanced radiotherapy could improve prostate cancer treatment.

In the UK, around 64,000 men are diagnosed with prostate cancer each year, and one in eight men will receive a prostate cancer diagnosis in their lifetime. These alarming statistics highlight the prevalence of prostate cancer and the critical need to deliver targeted treatments, driving research efforts worldwide. Recently, researchers in collaboration with the CLF’s Lasers for Science Facility (LSF) have been exploring incorporating tiny gold nanoparticles into cancer cells to increase the effectiveness of traditional radiotherapy.

Radiotherapy is used in approximately 50% of cancer patients because of its ability to employ X-ray radiation to kill cancer cells by lethally damaging their DNA (the genetic information which codes for living things) inside cells.

A significant drawback of its use is that it damages not only the cancerous tissue, but also the surrounding healthy tissue. This is particularly problematic when treating prostate cancer, as damage to close-by organs can lead to side effects such as bowel problems, incontinence, infertility and erectile dysfunction.

Much more than jewellery: gold’s ​​role in radiotherapy

​Due to its excellent biocompatibility, gold is well tolerated by human cells and tissues, underpinning its applications in dental restorations and medical implants. Gold also has a high atomic number, meaning it absorbs X-ray radiation exceptionally well compared to surrounding soft tissue. This absorption of X-rays results in an intense burst of electrons that deposit their energy nearby through a process called the photoelectric effect. As such, gold increases the sensitivity of tissue to radiotherapy and is termed a radiosensitiser.

Cancer cells need to take up more nutrients and material to sustain rapid, uncontrolled cell division, so when tiny flecks of gold are administered into the body, far more are absorbed by cancer cells than healthy cells. This results in an increase in the amount of radiation energy absorbed within the tumour volume, reducing radiation exposure to surrounding healthy tissue. Consequently, cancer patients could be provided with clear benefits of lower dose radiotherapy for shorter periods to reduce side effects on surrounding tissues and organs.

Despite their theoretical brilliance, there are significant delivery challenges associated with gold nanoparticles when used alone. They must be the correct size and prevented from agglomerating (sticking together) to move through the cell membrane. Free gold nanoparticles are around 800 times smaller than the width of a human hair (typically ranging between 1 and 100 nanometres (nm)), so they are rapidly cleared by the body and are too small to carry large quantities of gold into tumour cells.

To overcome this therapeutic barrier, scientists have developed a gold structure that can be absorbed by cancer cells effectively. This solution involves incorporating gold nanoparticles into larger engineered structures known as nanocomposites.

Minuscule parti​​cles, big impact​

In this study, researchers combined various numbers and sizes of gold nanoparticles with silica to create complex 50nm nanocomposites. Studying nanocomposites requires advanced microscopes at specialist facilities, such as the CLF’s Lasers for S​cience Facility (LSF), to research and validate their structure and behaviour.

(Image: Some of the paper’s authors standing outside the building where the CLF experiment took place. Left to right: Zengchun Xie, Jonathan Coulter, Susan Quinn, Mukesh K. Kumawat, Stan Botchway.)

Prof. Jonathan A. Coulter and Mukesh K. Kumawat (Queen’s University Belfast) and Prof. Susan J. Quinn and Zengchun Xie (University College Dublin) worked with the CLF’s LSF to study three types of silica-gold nanocomposites. The study aimed to optimise gold uptake and radiotherapy effects by varying the amount and location of gold nanoparticles within silica-gold nanocomposites.

The silica acts as a scaffold to hold the gold in place, overcoming the stability and agglomeration issues associated with free gold nanoparticles, enabling more gold nanocomposites to accumulate within the tumour volume. This means that local X-ray absorption by gold is increased, resulting in more effective radiotherapy.

Striking gold: the res​​ults

Nanocomposites were tested on two specific types of prostate cancer cell lines (PC3 and DU145), showing extremely promising results.

Using multiple advanced microscopy techniques simultaneously (electron and laser-based microscopy imaging) at the CLF’s Octopus imaging cluster (part of the LSF), the team were able to identify the most effective gold nanocomposite structure for treating prostate cancer cells. By more than doubling radiotherapy effectiveness in PC3 and more than tripling it in DU145, Au/SiAuC shone through as the best nanocomposite candidate. Its structure consisted of a gold core inside a silica scaffold with smaller gold particles on the scaffolding surface.

​The cross-section schematic shows the​ Au/SiAuC nanocomposite. It illustrates a 20 nm spherical, gold core inside a spherical silica scaffold, with many smaller 4 nm gold nanoparticles (AuNPs) shown on the silica scaffold surface. This nanocomposite structure is represented as described in the ACS Applied Nano Materials paper “Silica-Gold Nanocomposites Enhance Uptake and Radiosensitization in Prostate Cancer Cell Models”

Au/SiAuC was absorbed fastest, with an uptake speed more than four to five times greater than free gold nanoparticles. This structure also doubled the total gold found in prostate cancer cells after 24 hours, critical for heightening the potency of radiotherapy without increased side effects.

Crucially, nanocomposites were reproducibly synthesised and remained stable for at least four weeks in water. Moreover, scientists were able to show that, even at exceptionally high concentrations of gold nanocomposites, more than 80% of healthy cells survived. This is well above the 70% survival threshold for medical devices, highlighting gold’s non-toxic chemistry in the body and reinforcing its relevance in medical treatments.

A shimmering fu​ture?

So far, this technique has only been tested on prostate cancer cell models in a lab (an approach known as in vitro). While no doubt exciting, this research has explored nano-radiosensitisers at late preclinical to early clinical stages, so there is still some way to go before the technique routinely reaches patients.

Further studies will assess if the gold treatment remains safe and effective in living, biological organisms (in vivo), which pose significantly more gold delivery challenges than cell models. Should future large-scale clinical trials prove successful, gold nanoparticles could help to deliver the next gold standard in prostate cancer treatment.

(Image: Zengchun Xie and Mukesh K. Kumawat working in the CLF’s Octopus lab)

This work took place alongside parallel radiotherapy enhancement studies in other cancer types near vital organs, such as breast and glioblastoma (brain) cancers. As research progresses worldwide, gold could turn out to be an unexpected treasure in the fight against cancer.

This project was funded by the All-island North–South Research Programme (an initiative of the Higher Education Authority of Ireland TRACER project) and Research Ireland, SSPC grant 12/RC/2275_P2.

Visit the ACS Applied Nano Materials paper “Silic​a-Gold Nanocomposites Enhance Uptake and Radiosensitization in Prostate Cancer Cell Models”.