May 26, 2021
In the world of cancer therapies, nanoparticles hold great promise for delivering more effective and safer cancer treatment than the standard small molecule drugs that are commonly used today.
UNC Eshelman School of Pharmacy expert in the pharmacology of nanoparticles, William Zamboni, Pharm.D., Ph.D., is hoping to fight difficult-to-treat cancers using the combination of a novel type of radiation and nanoparticles, with the help of a five-year, $2,792,913 grant from the National Institutes of Health’s National Cancer Institute. The grant will support his research: “Minibeam Radiation Therapy (MRT) Enhanced Delivery of Nanoparticle Anticancer Agents to Pancreatic Cancer Tumors.”
“The promise of nanoparticle anticancer drugs remains largely unfulfilled due to relatively low tumor delivery, in which only 5-10% of these nanoparticle agents in the plasma are actually distributed into solid tumors,” Zamboni said.
Because of this, Zamboni said there is a strong need to discover methods that can capitalize on the promise of nanoparticle anticancer drugs by significantly and safely enhancing tumor delivery, especially in pancreatic cancer that has major inherent barriers to tumor delivery that are associated with high resistance and low response.
“A key issue for all patients with solid tumors is to get a higher delivery of the anticancer agents to the tumor versus normal tissues to improve efficacy and reduce toxicity. Our proposed studies are very exciting as these methods may also be used to enhance the tumor delivery of nanoparticles and other chemotherapeutic and biologic anticancer agents. Ultimately, if the anticancer agents do not reach the tumor and achieve therapeutic exposures they will not work,” said Zamboni, who works in the School’s Division of Pharmacotherapy and Experimental Therapeutics, Molecular Therapeutics Program at the UNC Lineberger Comprehensive Cancer Center, and is the director of the UNC Advanced Translational Pharmacology and Analytical Chemistry (ATPAC) Lab.
Zamboni is partnering with Sha Chang, Ph.D. at UNC and Steven Libutti, MD, FACS at Rutgers Cancer Institute of New Jersey, on the project. Zamboni said, “What is great about UNC in general and my colleagues Sha Chang and Steve Libutti, is the extreme willingness and selflessness to build a team of investigators that each bring their expertise to the project so that the project has the highest likelihood of being successful and ultimately improving the lives of patients with cancer.”
Zamboni, Chang, and Libutti, along with a multidisciplinary research team, will evaluate if induction minibeam radiation therapy, in contrast to conventional broad beam radiation therapy, increases tumor perfusion (the passage of blood or other fluid like cancer treatments, through blood vessels), and the tumor delivery and efficacy of nanoparticles in pancreatic cancer tumor models.
“The collaborative work we’ve done with breast cancer laboratory models using this approach will be translated to our work with pancreatic cancer where barriers to nanoparticle delivery are extensive. Surgical resection is the only curative option for pancreatic cancer – but only 15% of patients have resectable disease. A combination of minibeam radiation therapy with the nanoparticle regimen would afford an ideal pre-surgical treatment to promote better patient outcomes. We are hopeful this groundbreaking work will lead to human trials,” said Libutti, who is director of the Rutgers Cancer Institute and senior vice president of oncology services for RWJBarnabas Health.
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