Novel nanoscintillator concept leads to improved outcomes in pancreatic cancer
Research from the lab of Sunil Krishnan, MD, professor and John P. and Kathrine G. McGovern Distinguished Chair in the Vivian L. Smith Department of Neurosurgery, seeking to push the limits of light-activated therapies used to kill cancer cells has been published in Science Advances.
The paper, titled “Systemic antitumor immune response of doped yttria nanoscintillators under low-dose x-ray irradiation,” can be read here.
“We sought to overcome a challenge faced in clinical adoption of light-activated therapies wherein light only reaches a depth of a few millimeters within tissues and is unable to access deep-seated tissues,” said Krishnan, co-director of the Therapeutics and Pharmacology Graduate Program at The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences. “That limits the reach of light-activated therapies such as photodynamic therapy where light triggers a photosensitizer in tumors to generate free radicals that kill the cancer cells or photothermal therapy where light activates a molecule or a nanoparticle in tissues to generate heat to burn blood vessels or tumors.”
The lab theorized that x-rays could reach any target in the body with their ability to travel deeper and wondered if they could convert those x-rays into light within the body. To test this theory, they created a nanoscintillator, which was coated with a photosensitizer that could reach a pancreatic tumor. When triggered by radiation, the nanoscintillator-photosensitizer complex would emit light to generate free radicals and kill the cancer cells in the tumor.
The theory was born from the original research of current McGovern Medical School student Onur Sahin, who created a number of nanoscintillators by using a variety of recipes during his time as a graduate student at Rice University.
“The challenge was to find one that efficiently converts x-rays to light, potentially has an afterglow after the x-ray is switched off, and can be scaled down to a nanoparticle size while retaining efficient light generation capability,” Krishnan said.
After creating a prototype that fit the need of the research, the lab treated cells in culture with both the nanoconstruct and radiation and discovered that the combination led to more cell death than treatment with just radiation alone or the nanoconstruct alone. Next, they tested the nanoconstruct and radiation in a murine model which showed similar results of tumor growth regression.
As a final test, the group added immunotherapy to the treatment which helped lead to even greater tumor growth regression of both the irradiated tumor and of an additional tumor that was growing away from the site of radiation. These results are important for diseases such as pancreatic cancer which typically have metastases that are not readily visible on imaging.
“If a localized treatment to the primary tumor can also eradicate occult metastases, it could increase long-term survival of patients with a notoriously deceptive tumor like pancreatic cancer,” Krishnan said.
From the research, the lab was able to conclude that x-ray activated photodynamic therapy may be a viable treatment option for pancreatic cancers, and additionally, coupling this treatment with immunotherapy may stimulate a more robust immune response against occult metastases.
“We are excited that we have found a way to enable light-activated therapies in deep-seated tumors,” Krishnan said. “We hope to build on this platform to trigger other light-activated therapies like photothermal therapy, photoactivated nanomachines, photocleavable linkers, optogenetics, and others.”