Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP; La Jolla, CA) have developed a proof-of-concept nanosystem that dramatically improves the visualization of tumors. The platform achieves a five-fold increase over existing tumor-specific optical imaging methods, generating bright tumor signals by delivering quantum dots (QDs; tiny particles that emit intense fluorescent signals when exposed to light) to cancer cells without any toxic effects.
The platform pairs QDs and an etchant that eliminates background signals. The QDs are delivered intravenously, and some of them leave the bloodstream and cross membranes, entering cancer cells. Fluorescent signals emitted from excess QDs that remain in the bloodstream are then made invisible by injecting the etchant.
The etchant and the QDs undergo a "cation exchange" that occurs when zinc in the QDs is swapped for silver in the etchant. Silver-containing QDs lose their fluorescent capabilities, and because the etchant cannot cross membranes to reach tumor cells, the QDs that have reached the tumor remain fluorescent. Thus, the entire process eliminates background fluorescence while preserving tumor-specific signals.
The method was developed using mice harboring human breast, prostate, and gastric tumors. QDs were actively delivered to tumors using iRGD, a tumor-penetrating peptide that activates a transport pathway that drives the peptide along with bystander molecules—in this case, fluorescent QDs—into cancer cells.
"We are encouraged that we were able to achieve a tumor-specific contrast index (CI) between five- and ten-fold greater than the general cut-off for optical imaging, which is 2.5," says Kazuki Sugahara, MD, Ph.D., an adjunct assistant professor at SBP and adjunct associate research scientist at Columbia University (New York, NY), whose lab developed the method.
"Moving forward, we will focus on developing our novel nanosystem to work with routine imaging tests like PET scans and MRIs. In our studies with mice, we use optical imaging, which isn't always practical for humans," Sugahara explains.
A new company is in the process of being founded to further develop the platform for human use.
Full details of the work appear in the journal Nature Communications.
For more information, please visit www.sbpdiscovery.org.