Yuan Lin, Ph.D.

Nanoparticles to Deliver Cancer Immunotherapy?


FUNDED BY: The generosity of various 2017 SPARK Donors

What was the goal of your SPARK project?

With solid tumor cancers, the challenge for the immune system is both to identify and then successfully attack the tumor. Recent cancer immunotherapies involving immune checkpoint inhibitors have had success in yanking away tumor cells’ “invisibility cloak”. However, one of the protective molecules deployed by tumors, adenosine, accumulates in such high concentrations that it can render the immunotherapy ineffective. This suggests that multiple immune suppression mechanisms co-exist and there might be a benefit to combining adenosine blockers (ARIs) with existing check-point immunotherapies. There are several ARI drugs in development, however the challenge remains to design a tool that delivers these drugs in a manner that allows them to counteract the high concentration of adenosine. This SPARK project was to determine if nanoparticles could be used as an effective delivery mechanism for ARIs.

SPARK project results:

For this project, we wanted to test our hypothesis that by using nanoparticles to deliver ARIs, we could more effectively deliver high amounts of ARIs to tumors to shrink and ultimately kill them. We used SPARK funding to combine a particular ARI (SCH58261) with a fluorescent dye and encapsulate them together in a biodegradable polymer to create drug-eluting nanoparticles, which, once injected into a tumor, result in a slow, localized drug release. We then used fluorescence microscopy and flow cytometry to visualize the fluorescent dye first in cell culture to help determine which immune cells take up nanoparticles, and then in vivo in tumor-bearing mice to determine its effectiveness in reducing tumor size. When we analyzed the uptake of nanoparticles in mouse immune cells and then human immune cells, we identified phagocytic macrophages as the primary target for nanoparticle uptake in both. We then moved on to investigating in vivo update of nanoparticles, and found that virtually all of the particles remained at the site of injection and that no fluorescence could be detected outside of the tumor, suggesting that intratumoral injection of nanoparticles could be used to localize drugs within tumors to improve potency and reduce toxicity. Further studies found that our ARI-loaded nanoparticles could more effectively reduce tumor size in mice.

What’s next for this project?

The findings from this SPARK-funded experiment have great potential for clinical translation since encapsulation of ARI drugs into nanoparticles may prove to be safer and more effective than orally administered ARIs currently in clinical trials. The future work is to test more nanoparticles to find the best composition used for drug loading. I applied for a grant for follow-up studies with the National Institutes of Health as a result of the preliminary results from this project.