Novel nanoparticle delivers cancer therapy, fluoresces when cells die

Researchers at Brigham and Women's Hospital (BWH; Boston, MA) have developed a nanoparticle that delivers a drug and then fluoresces green when cancer cells begin dying, allowing them to visualize whether a tumor is resistant or susceptible to a particular treatment much sooner than currently available clinical methods. They tested their approach in preclinical models, which could someday offer physicians a readout on the effectiveness of chemotherapy in as few as eight hours after treatment. The technology could also be used for monitoring the effectiveness of immunotherapy.

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The approach takes advantage of the fact that when cells die, a particular enzyme known as caspase is activated. The researchers designed a reporter element that, when in the presence of activated caspase, fluoresces green. The team then tested whether they could use the reporter nanoparticles to distinguish between drug-sensitive and -resistant tumors. Using nanoparticles loaded with anti-cancer drugs, the team tested a common chemotherapeutic agent, paclitaxel, in a preclinical model of prostate cancer and, separately, an immunotherapy that targets PD-L 1 in a preclinical model of melanoma. In the tumors that were sensitive to paclitaxel, the team saw an approximately 400% increase in fluorescence compared to tumors that were not sensitive to the drug. The team also saw a significant increase in the fluorescent signal in tumors treated with the anti-PD-L1 nanoparticles after five days.

"We've demonstrated that this technique can help us directly visualize and measure the responsiveness of tumors to both types of drugs," says co-corresponding author Ashish Kulkarni, an instructor in the Division of Biomedical Engineering at BWH. "Current techniques, which rely on measurements of the size or metabolic state of the tumor, are sometimes unable to detect the effectiveness of an immunotherapeutic agent as the volume of the tumor may actually increase as immune cells begin to flood in to attack the tumor. Reporter nanoparticles, however, can give us an accurate read out of whether or not cancer cells are dying."

The research team now plans to focus on the design of radiotracers that can be used in humans, and tests of both safety and efficacy will be necessary before the current technique can be translated into clinical applications. Co-corresponding author Shiladitya Sengupta, PhD, a principal investigator in BWH's Division of Bioengineering, Kulkarni, and their colleagues are actively working on these steps to further the lab's goal of improving the management and treatment of cancer using nanotechnology.

Full details of the work appear in the Proceedings of the National Academy of Sciences; for more information, please visit http://dx.doi.org/10.1073/pnas.1603455113.