A nanoparticle that targets melanoma and highlights cancerous tissue is entering an early-stage clinical trial. Researchers testing the nanotherapeutic agent, which has been under development for over a decade, hope it provides a way to target melanoma and map its spread throughout the body. Researchers have tested the drug in animals and found no toxicity. Safety tests in five melanoma patients should be completed by the end of the year.
Drugs that help doctors image, characterize, and treat diseases could result in treatments that are better targeted to an individual patient's disease. "With cancer genome programs, we're learning more and more about differences between individuals' diseases," says Jerry Lee, director of the Office of Physical Sciences-Oncology at the National Cancer Institute. That information will tell doctors what drugs will work best for a patient, and how they might best be delivered. "Multifunctional, tailored nanoplatforms will bridge with that biological information," enabling doctors to act on it to improve patient care, Lee says.
The new melanoma-targeting nanoparticles were developed by Ulrich Wiesner, professor of materials science at Cornell. He's worked with a group led by Michelle Bradbury, a radiologist at the Memorial Sloan-Kettering Institute in New York City, to test the nanoparticles in animals. Bradbury is also leading the clinical trial.
The researchers hope to use the nanoparticles to address two major clinical needs. First, they want to use it to develop a therapy that seeks out melanoma tumors. "There's never been a targeted therapy for melanoma," says Bradbury. Melanoma starts on the skin, but when it spreads to other parts of the body, it is invisible and deadly. A targeted therapy would seek melanoma out no matter where it has spread.
"Another gap in the field is the lack of an optical imaging agent to visualize lymph nodes," says Bradbury. Today, surgeons use radioactive labels and a handheld gamma detector to find cancer-carrying lymph nodes in the head and neck during surgery. But this is a tricky process. Bradbury hopes the nano-imaging agent can be used to light up cancer-carrying lymph nodes during surgery, providing a map that helps doctors remove the cancer while avoiding unnecessary cutting that can lead to painful side effects.
The core of the nanoparticles is a silica sphere, about eight nanometers in diameter, surrounding an organic dye molecule that emits infrared light. This is then coated with a biocompatible polymer that helps the nanoparticles stick around in the body. Wiesner and a former student first developed the nanoparticles over 10 years ago. The nanoparticles are made by a company called Hybrid Silica Technologies. The coated nanoparticles can be modified to serve many different purposes. "Through simple biochemistry, you can attach peptides to target tumors, drugs, and radioactive imaging labels," says Wiesner.
For the initial patient trial, Wiesner and Hybrid Silica Technologies provided the clinical researchers with the nanoparticles. The nanoparticles were treated with radioactive iodine in order to make them visible on PET scans. The advantage of PET scans is their incredible sensitivity, says Bradbury. If an MRI label were added to the particle and that imaging technique were used instead, a much higher dose would be necessary. "PET enables you to do microdosing," she says. PET scans help provide a very detailed map of where the nanoparticles travel inside the body.
Bradbury hopes that oncologists will eventually use this type of imaging to better understand a patient's disease. PET imaging is sensitive enough to allow researchers to estimate how many of different types of receptors are present on an individual tumor's cells, information that should help doctors determine how aggressive a tumor is, where it might spread and when, and how it should be treated.
However, this type of agent must strike the right balance between remaining in the body long enough to do its work but not overstaying its welcome. "It remains in the blood for enough time to target the tumor, yet clears through the kidneys efficiently," says Bradbury. Drugs that move through the liver stay in the body longer and can get broken down into potentially toxic side-products. In mice, the silica particles are excreted in about 24 hours. Ten years of tests in animals have shown no toxicity.
"If we can get these into the clinic, this is a platform that could really expand what we can do for patients," says Bradbury.
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