Cancer treatment with gold nanoparticles can kill tumors and spare healthy tissue, shows clinical trial
The first-ever prostate cancer treatment, which uses gold nanoparticles to destroy tumorous cells, without damaging healthy tissue, has crossed a major milestone. Thirteen of the first 15 prostate cancer patients - who were treated in a clinical trial of the nanoparticle-based, focal therapy (focused therapy that destroys cancer while sparing the rest of the prostate) - showed no detectable signs of cancer a year after treatment. This is a major development in the decades-long quest by a team of researchers to develop a treatment that kills tumors without the debilitating side effects of chemotherapy, invasive surgery, and radiation, according to the findings published in the Proceedings of the National Academy of Sciences (PNAS).
The paper presents the results from patients - initially 16 - who were treated at the Icahn School of Medicine at Mount Sinai in New York. According to the researchers, it is believed to be the first published clinical study of “photothermal cancer therapy” - one that uses illuminated nanoparticles to heat and destroy tumors - in a refereed scientific journal.
“There’s a bigger picture here. This (study) is 16 men, but when does it get to be 16,000? Sixteen million? Because 1 in 9 men are going to have to deal with this in their lifetime. The thought that this treatment could alleviate the side effects, and the misery that my dad experienced is truly heartwarming,” says Rice University engineer and nanoscientist Naomi Halas, who invented the nanoparticles at Rice in 1997.
The trial, which is ongoing and has treated 44 patients at Mount Sinai and two other clinical sites in Michigan and Texas, is the culmination of a 20-year pursuit by Halas and Duke University bioengineer Jennifer West.
Halas and West, co-authors of the new study, first envisioned the nanoparticle-based therapy around 2000 while working together in Rice’s Brown School of Engineering. Back then, the work generated a lot of interest and had garnered national awards. By the early 2000s, Halas and West had co-founded a Houston-based startup, Nanospectra Biosciences, to develop the technology for clinical use.
During that time, Halas’ father, who was 85-years-old, was diagnosed with prostate cancer. According to Halas, her father had ‘profound’ hearing loss and was legally blind. Two years after his radiation therapy, it became almost impossible for him to urinate. According to Halas, it is because of her father that she knows a lot about what people with prostate cancer go through. “He was in and out of the hospital weekly. The doctor would catheterize him. He would go home. Things would be fine for a few days, and then he’d have to go to the emergency room. It was unbelievable what he went through,” says Halas.
At the time, Nanospectra was conducting the necessary pre-clinical work to show that nanoshells could be safely used in humans. Halas’ father died many years ago, but she recalls a conversation that continues to motivate her. He had told her, “If you could prevent just one person from having to go through the hell that I went through, it would be worth it.”
What do the numbers say?
According to the American Cancer Society, other than skin cancer, prostate cancer is the most common cancer in American men, and about one man in 9 will be diagnosed with prostate cancer during his lifetime. Further, prostate cancer is the second leading cause of cancer death in American men, behind lung cancer, and about one man in 41 will die of prostate cancer. The American Cancer Society estimates about 174,650 new cases of prostate cancer and approximately 31,620 deaths from prostate cancer in 2019.
Prostate cancer begins when cells in a male’s prostate gland start to grow uncontrollably. According to experts, the side effects of prostate cancer can be extremely traumatic. Treatment options have traditionally included radical prostatectomy, which is the removal of the prostate gland and some of the tissue around it; radiation therapy; and chemotherapy, among others. These methods carry the potential to have a negative impact on urinary function and sexual performance, say experts.
What are these nanoparticles?
The nanoparticles, called nanoshells, are made of small layers of silica glass formed into a sphere and wrapped in a thin layer of gold. They are about 50 times smaller than a red blood cell. By varying the thickness of the gold shell, Halas had shown she could tune nanoshells to interact with specific wavelengths of light. Around 2000, she and West invented a method of destroying cancer cells by heating nanoshells with a low-power, near-infrared laser that could pass harmlessly through healthy tissue.
The nanoshells convert light into heat and thermally destroy solid tumors without damaging adjacent healthy tissue. The scientists explain that the nanoparticles are special in that one can design a nanoparticle to absorb light at wavelengths that pass directly through the body. So, if the particles are placed in a tumor site, one can irradiate them with light that penetrates through the body. The nanoparticles will absorb the light, convert the light to heat and then, very gently, they will induce hyperthermia and destroy just the tumor cells, which they are directly adjacent to. Hence, this can be used as a vehicle for highly localized photothermal ablation of cancer, the team says.
Getting FDA approval was tough
From the outset, West and Halas had visualized a treatment that would destroy cancer without the painful side effects often associated with chemotherapy, invasive surgery, and radiation. And that had been borne out in their early studies in cell cultures and mice. “The science has not changed. If you look back to our original paper, where we did the first animal studies, there is nothing fundamentally different in the science,” says West.
But getting clinical trials approved by the Food and Drug Administration (FDA) was not easy, in part because the technology was groundbreaking, says the research team. “We were the first, really engineered nanoparticle to go into human beings. In the beginning, the FDA was not sure how to handle these types of materials. We had something that looked like an injectable liquid in an IV bag. Was it a drug or a device? There was a point in time where the FDA was discussing creating a whole new division just for nano,” explains West.
However, says the team, the FDA decided to regulate the treatment, which Nanospectra branded as AuroLase Therapy, as a medical device. Clinical trials focused on safety began nearly 10 years ago with a study in late-stage head and neck cancer. According to the researchers, Nanospectra learned valuable lessons at every step, but it was another big advance - one in medical imaging - that set the stage for the success in prostate cancer.
In 2011, researchers from the National Institutes of Health published results of a new technique that combined ultrasound and MRI imaging to resolve prostate tumors with millimeter-scale precision. Clinicians began adopting the technique for “fusion biopsies,” a procedure for targeting needle biopsies to the specific site of suspected tumors.
The researchers say that one of the lead researchers working to develop fusion biopsy technology - Ardeshir Rastinehad - joined Mount Sinai in 2015 and was an “early proponent of using the fusion imaging platform for focal therapy, a minimally invasive treatment that could target tumors without the risks of incontinence and impotency”, which were associated with whole-gland treatments like surgical removal of the prostate or radiation.
Current therapy could be life-changing
Sixteen men, who were aged 58 to 79 years and had low- to intermediate-risk localized prostate cancer, agreed to participate in a trial of AuroLase Therapy, a “focal ablation treatment” that uses gold nanoparticles to heat and destroy tumors.
Fifteen of the 16 patients underwent a two-day treatment. One day after treatment, guided by magnetic resonance-ultrasound (MR/US) fusion imaging, a laser catheter housing an optical fiber was used to deliver near-infrared light through thin tubes inserted into the prostate, heating the nanoshells. None of the patients reported serious side effects during the procedure or at the 90-day follow-up. At 12 months, MR/US fusion biopsies revealed that the vast majority of treated lesions showed no evidence of tumor in the ablation zone.
“They received an intravenous infusion of nanoparticles on day one and underwent an image-guided ablation treatment on day two", the findings state. All of the patients went home on the day of the treatment and returned for follow-up tests at three months, six months, and one year after the treatment.
The researchers say the gold nanoparticles act as tumor-seeking missiles. They seek out cancer cells and enter them. The researchers use laser light to excite the nanoparticles, make them vibrate and pulse with extreme temperatures, which kills the cancerous tissue.
“The shells seek out and saturate cancerous cells, and their advanced vibrational properties are then harnessed to cause the tumorous tissue to pulse with extreme temperature when light is applied through a laser specifically designed to excite the particles. The oscillation kills the cancer cells while preserving the healthy tissue, avoiding the nerves and urinary sphincter. This procedure is the first in the world that is precise enough to potentially avoid side effects such as urinary incontinence or sexual impotency,” the findings state.
Of the 15 who completed treatment, only two showed detectable signs of cancer in follow-up biopsies and MRIs one year later, says the study. “Gold-silica nanoshell infusion allows for a focused therapy that treats cancer while sparing the rest of the prostate, thus preserving a patient’s quality of life by reducing unwanted side effects, which could include erectile dysfunction and/or the leakage of urine,” says lead author and trial principal investigator Rastinehad, Associate Professor of Urology and Radiology at the Icahn School of Medicine at Mount Sinai.
According to the research team, the results demonstrate what is possible when physicians and engineers work together to solve problems. “This work demonstrates the power of collaboration across engineering and medicine. It shows how collaboration can enable the translation of exciting new technologies into clinical medicine to improve the lives of patients,” says West.