Published by the Students of Johns Hopkins since 1896
December 8, 2021

Nanoparticles treat brain tumors

By Mo-Yu Zhou | April 27, 2012

A new technique involving nanoparticles has exciting potential benefits for brain cancer patients. According to a recent study by scientists at the Stanford University School of Medicine, the tiny particles can be imaged in three ways to facilitate and guide the removal of brain tumors from mice.
Led by Sam Gambhir of the Radiology Department, the team of scientists engineered nanoparticles that detected and highlighted brain tumors. By offering a precise way of determining the boundaries of the tumor, the method can be used to remove brain tumors with unprecedented accuracy.
The most serious kind of brain tumor is glioblastoma, of which 3,000 cases are diagnosed annually. Without treatment, patients with glioblastoma are expected to die within three months. Whenever possible, such tumors are removed, but this procedure only prolongs the patient's life by about one year, since even the best neurosurgeons find it almost impossible to remove the whole tumor without sacrificing healthy brain.
This lack of precision is an especially large problem when one considers the shape of these tumors, which are typically rough, with tiny fingerlike protrusions that follow blood vessels and nerves. In addition, the primary tumor can, while replicating and migrating cells, produce tiny tumor patches called micrometastases, which are nearly invisible to the surgeon's eye and can infiltrate otherwise healthy tissue. The micrometastases can then grow into new tumors.
This study used what were essentially imaging reagents coated on minuscule gold balls, each measuring less than five one-millionths of an inch in diameter. The scientists hoped that injecting these nanoparticles intravenously would cause them to seek out tumors but leave healthy brain tissue alone. Since the blood vessels that feed brain tumors are quite permeable, the particles would escape from the vessels and attach themselves to the tumor. Thanks to the gold cores of the particles, they would then be visible to each of three imaging techniques.
The first kind is magnetic resonance imaging (MRI), which surgeons already commonly use to gauge where the tumor is likely to be before they operate. The nanoparticles are coated with an MRI contrast agent, gadolinium. However, while MRI can determine a tumor's boundaries, it is used preoperatively and therefore cannot perfectly describe the tumor at the time of operation, given the dynamic nature of both the tumor and the brain.
The second kind of imaging used is called photoacoustic imaging. The nanoparticles' gold cores absorb pulses of light and produce ultrasound signals that allow for the creation of a three-dimensional image of the tumor.
The third, Raman imaging, uses materials in the coating of the particles to give off small amounts of light produced in a specific pattern of wavelengths. The weak signals are amplified by the gold cores, and can then be captured by a special microscope.
The scientists began by showing that the nanoparticles targeted only tumor tissue and not healthy tissue. They then implanted different types of human glioblastoma cells into the brains of mice. Injecting the nanoparticles into the tail veins of the mice, the scientists were able to use all three imaging methods to visualize the tumor. The MRI scans and photoacoustic images were able to produce accurate images of the tumor pre-operation and during the operation, respectively. The bulk of the animal's tumor was initially cleared using these first two methods.
However, to produce sufficiently precise detail, the sensitive Raman images proved to be critical. Because Raman signals were only produced by nanoparticles, after the clearing of most of the tumor, this third technique was used to flag and then remove any residual micrometastases and fingerlike projections in adjacent normal tissue.
This technique offers hope for the field of brain cancer treatment, allowing for the precisely controlled removal of both the tumor and residual tumor material. According to Gambhir, the technique might even someday be used to treat other types of tumors.

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