Surgical procedures are used to remove cancerous tumors from the body, but are less invasive procedures possible? Sason Torosean, a researcher at Dartmouth College, attempted to answer in a biophysics seminar last Thursday at Wilder Hall. Torosean, along with other researchers, developed a new ultrasound and fluorescence hybrid system that can be used to monitor drug delivery and distribution in tumor cells.
“We want to understand drug therapy,” Torosean says, “because we don’t think the drugs always reach the tumors.” Although drug treatments are used to treat tumors, it is uncertain whether the drug can effectively reach its target tissue. However, ultrasound and fluorescent imaging can be used to monitor the activity of nanoparticles in tumor cells.
“We used ultrasound to find where the tumor is,” Torosean explained. Using mice as experimental models, Torosean injected fluorescent nanoparticles into induced tumors in the mice. The injected nanoparticle was the drug ALA. When excited with a laser, ALA produces a toxin called PpIX that kills tumor cells.
The laser also induced fluorescence in the nanoparticle, allowing for imaging of the distribution of ALA molecules. Fluorescent wavelengths were taken from samples of both normal and tumor tissue and compared; the normalized measurements indicated how many nanoparticles were present in tumor tissues, based on their absorbance levels.
Torosean was also interested in studying the effects that physical parameters would have in limiting drug delivery. For example, interstitial fluid pressure, tumor stiffness, and vascular density were all known to affect drug concentration in tumor cells. These parameters were measured and then compared to the overall nanoparticle delivery for various tumor cells.
Torosean found that lower fluid pressure and stiffness resulted in higher nanoparticle delivery, and stiffness was also found to increase fluid pressure. Although increased vascular density would increase drug delivery, heightened fluid pressure would counteract this effect by killing off the growth of vessels in cells.
Overall, Torosean explained, “We showed that our measurements are consistent with the models.” In particular, a linear response between the absorbance of light and the concentration of PpIX was found, confirming a direct correlation between absorbance and concentration. The relationships between nanoparticle delivery and known physical barriers in tumors were also elucidated.
“The project has some definite clinical applications,” says Torosean, “and can be used to replace invasive surgical procedures.” By locating tumors and measuring drug concentration using a novel combination of both ultrasound and fluorescent imaging, a safer and more efficient alternative to surgery may soon be introduced.