Gold nanoshell-based cancer treatment is safe for the clinic

Nanoparticles tuned to absorb near-infrared radiation heat the tumour while sparing surrounding tissue

Original source: Physics World

Prostate cancer can be treated using nanoparticle-based photothermal therapy without triggering severe side effects. This is the conclusion of a year-long clinical trial conducted at Icahn School of Medicine at Mount Sinai, where prostate-cancer patients were injected with gold–silica nanoparticles and irradiated locally using near-infrared lasers.

In the 90 days post-treatment, none of the subjects suffered serious side effects, fulfilling the aim of the trial. Although the treatment’s efficacy was not formally measured, the results are encouraging: biopsies showed that 13 of the 16 patients who underwent the procedure were cancer-free after 12 months (PNAS 10.1073/pnas.1906929116).

Current non-surgical treatments for prostate cancer are highly effective but can cause damage to healthy tissue surrounding the tumour. Thermal therapies like focused ultrasound and focal laser ablation, for example, can raise temperatures outside of the treatment volume, while even precisely targeted radiotherapy imposes an unavoidable radiation burden along the length of the beam path. This damage can lead to quality-of-life-limiting side effects such as erectile dysfunction and urinary incontinence. In order to avoid such adverse effects, Ardeshir Rastinehad and colleagues across the US are exploring an alternative method that is intrinsically harmless to tissue outside of the tumour.

The approach taken by the team exploits a phenomenon called surface plasmon resonance, whereby surface electrons in a metal strongly absorb electromagnetic radiation. Nanoparticles consisting of gold shells around silica cores can be tuned to absorb a given frequency of radiation by fabricating them with specific dimensions. When the gold shells are 150 nm across, they absorb in the near-infrared (NIR), a frequency at which tissue is nearly transparent.

The researchers injected solutions of these gold–silica nanoshells (GSNs) into patients intravenously. Prostate tumours typically have abnormally formed vascular systems, making them “leaky”. This means that, although the GSNs are introduced into the patient’s general circulatory system, within the tumour they pass through gaps in the vessel walls and become concentrated in the cancerous tissue.

Next, guided by a combination of MRI and ultrasound, the team inserted enough optical fibres to achieve full coverage of the tumour volume (between four and 21 fibres in this trial). When the tumour is illuminated by NIR lasers via the optical fibres, the GSNs absorb the radiation and heat up. The aim is to ablate the tumour by increasing its temperature to 55–65 °C for a minute and a half. As the surrounding healthy tissue is less thoroughly perfused with GSNs, it absorbs the NIR radiation much less strongly, and therefore suffers no permanent effects.

As the researchers hoped, side effects from the procedure were relatively minor, with no cases reaching the level of “severe” according to the Common Terminology Criteria for Adverse Events (CTCAE) in the first three months. Throughout the entire year-long follow-up period, participants reported no significant changes across a range of criteria including measures of quality-of-life, erectile dysfunction and urinary symptoms.

As well as effectively sparing patients from severe adverse reactions, GSN-based photothermal therapy also performed well at tumour control: at three months, the lesion sites tested negative for cancer in ten of the 16 subjects, and by 12 months this had risen to 14 of the 16. Despite these promising results, Rastinehad and colleagues can report no formal assessment of the treatment’s efficacy, as the clinical trial involved too few subjects.

“The reason efficacy was not the focus of this paper was that we need 45 patients to be completed to be able to reliably report efficacy,” says Rastinehad. “We have actually accrued the patients needed and are currently waiting for all the data to be collected. That data should be available sometime next year.”