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.