Golden Bullet for Cancer? Nanoparticles Provide Targeted Version of Photothermal Therapy for Cancer (Cont'd)
Passive targeting
"If we put bare nanoparticles into your body," says Xia, "proteins would deposit on the particles, and they would be captured by the immune system and dragged out of the bloodstream into the liver or spleen."
To prevent this, the lab coated the nanocages with a layer of PEG, a nontoxic chemical most people have encountered in the form of the laxatives GoLyTELY or MiraLAX. PEG resists the adsorption of proteins, in effect disguising the nanoparticles so that the immune system cannot recognize them.
Instead of being swept from the bloodstream, the disguised particles circulate long enough to accumulate in tumors.
A growing tumor must develop its own blood supply to prevent its core from being starved of oxygen and nutrients. But tumor vessels are as aberrant as tumor cells. They have irregular diameters and abnormal branching patterns, but most importantly, they have thin, leaky walls.
The cells that line a tumor's blood vessel, normally packed so tightly they form a waterproof barrier, are disorganized and irregularly shaped, and there are gaps between them.
The nanocages infiltrate through those gaps efficiently enough that they turn the surface of the normally pinkish tumor black.
A trial run
In Welch's lab, mice bearing tumors on both flanks were randomly divided into two groups. The mice in one group were injected with the PEG-coated nanocages and those in the other with buffer solution. Several days later the right tumor of each animal was exposed to a diode laser for 10 minutes.
The team employed several different noninvasive imaging techniques to follow the effects of the therapy. (Welch is head of the oncologic imaging research program at the Siteman Cancer Center of Washington University School of Medicine and Barnes-Jewish Hospital and has worked on imaging agents and techniques for many years.)
During irradiation, thermal images of the mice were made with an infrared camera. As is true of cells in other animals that automatically regulate their body temperature, mouse cells function optimally only if the mouse's body temperature remains between 36.5 and 37.5 degrees Celsius (98 to 101 degrees Fahrenheit).
At temperatures above 42 degrees Celsius (107 degrees Fahrenheit) the cells begin to die as the proteins whose proper functioning maintains them begin to unfold.
In the nanocage-injected mice, the skin surface temperature increased rapidly from 32 degrees Celsius to 54 degrees C (129 degrees F).
In the buffer-injected mice, however, the surface temperature remained below 37 degrees Celsius (98.6 degrees Fahrenheit).
To see what effect this heating had on the tumors, the mice were injected with a radioactive tracer incorporated in a molecule similar to glucose, the main energy source in the body. Positron emission and computerized tomography (PET and CT) scans were used to record the concentration of the glucose lookalike in body tissues; the higher the glucose uptake, the greater the metabolic activity.
The tumors of nanocage-injected mice were significantly fainter on the PET scans than those of buffer-injected mice, indicating that many tumor cells were no longer functioning.
The tumors in the nanocage-treated mice were later found to have marked histological signs of cellular damage.
