Men with low-to-intermediate grade tumors face a tough choice, with treatment choices that have adverse effects. Although laser ablation has offered an avenue of hope, the U.S. FDA has advised of the potential for tissue overheating in connection with MR-guided, laser interstitial thermal therapy systems.

Now, Nanospectra Biosciences Inc., which is focusing on nanomedicine for selective thermal tissue ablation, reported the publication of first-in-human data of the company’s Aurolase therapy for the focal ablation of prostate tissue.

This milestone has been years in the making. “Jennifer West, bioengineer at Duke University, and I initiated development of the gold-silica nanoshells nearly 20 years ago,” said Naomi Halas, professor of biophysics at Rice University, gold-silica nanoparticles (GSN or Auroshells) inventor and original co-founder of Nanospectra Biosciences. “By varying the thickness of the gold outer shell, we demonstrated that we could tune the nanoshells to interact with specific wavelengths of light. By tuning the resonance beyond the visible and into the near-infrared region, we opened the door to a wide range of applications in nanomedicine.”

This pilot device study (NCT02680535) used laser-excited GSNs in combination with multiparametic MRI (mpMRI)/ultrasound (US) fusion imaging, to focally ablate low-to-intermediate grade tumors within the prostate. GSN are designed to absorb near-infrared light at wavelengths of high tissue transparency, converting the light energy to heat, and provide a new and highly localized light-based strategy for the treatment of prostate cancer with lowered risks of harmful treatment-related side effects.

The published results were from Mt. Sinai’s first 16 enrolled subjects. After GSN infusion and targeted laser ablation, patients underwent MRI of the prostate at 48 to 72 hours, followed by post-procedure mpMRI/US targeted fusion biopsies at three and 12 months, as well as a standard 12-core systematic biopsy at 12 months. GSN-mediated focal laser ablation was successfully achieved in 15 of the 16 patients. In addition, at the one-year study endpoint, 87.5% were negative for tumor.

No serious adverse events were seen during the procedure, and all patients were discharged the same day.

The authors of the study see great potential. “GSN-directed ablation builds on the initial lessons learned from LITT [laser interstitial thermal therapy], attempting to overcome some of the known limitations of laser ablative technology,” they wrote. Their findings were published Aug. 26, 2019, in the Proceedings of the National Academy of Sciences in a paper titled, “Gold Nanoshell-Localized Photothermal Ablation of Prostate Tumors in a Clinical Pilot Device Study.”

Optical properties

“They work as a function of their optical properties,” David Jorden, CEO of Nanospectra, told BioWorld MedTech when asked about the science behind the technology. “They’re infused into the body, and it’s natural tumor biology that allows for the preferential accumulation of the particles – the nanoshells in the leaky vasculature of tumors, which characterizes pretty much all solid tumors.”

Ultimately, the energy source used to ablate is delivered in the proximity of the shells. “The light transduces that gold into a sufficient increase in thermal temperature to create cell death, but it only does that where the particles are located, and, consequently, healthy tissue where particles would not be is going to be warmed, but not killed.”

When asked if anything really stood out for him with the study results, Jorden highlighted the lack of comorbidity problems.

“The real, I guess, crux of this would be that we arguably overtreat low-to-intermediate risk prostate cancer.” Traditionally, options for treating were prostate removal or radiation therapy, which have significant co-morbidities and adversely affect the patient’s quality of life.

“So, the whole premise here is: Hey, there is this big middle ground between active surveillance, which means you’re just monitoring the cancer for progression and so forth, and the radical treatment options. Can’t we develop some therapies that are effective from a cancer-control standpoint but yet leave the patient in essentially the same functional state as prior?” He noted that this study had that question embedded in it, adding that the patients’ functional outcomes have been very stable.

The technology could be used in other cancers, he said, adding that all solid tumors are based on the leaky vasculature phenomenon. For it to be operable in other parts of the body, the tumor site must have sufficient vascularity to allow the particles to accumulate. Location also is key.

The company is considering other parts of the body either after or concurrent with the final prostate study, which is slated to begin next month. Thyroid cancer is one potential area, as are retinal tumors and melanoma. “We want to be smart about the places where the real attributes of the technology – its focal nature – allow it to be most effective.”

In terms of going to the FDA for clearance of the device, the company is eyeing an early 2021 time frame. It hopes to gain the clearance by the middle of that year. Other geographies are being considered, including the EU, a region that Jorden said is even more accepting of the focal therapy approach than the U.S.