Reviewed by Lexie CornerMay 7 2024
In a recent study published in Proceedings of the National Academy of Sciences, scientists at the University of Miami Miller School of Medicine's Sylvester Comprehensive Cancer Center developed a nanoparticle that can deliver drugs to both breast tumors and brain metastases by crossing the blood-brain barrier.
“I always say nanomedicine is the future, but of course, we have already been in that future,” said Dr. Shanta Dhar, referring to commercially available COVID-19 vaccines, which use nanoparticles in their formulation. “Nanomedicine is definitely also the future for cancer therapeutics.” Image Credit: Sylvester
Their objective is to eradicate primary breast cancer tumors and brain metastases in a single treatment, and their research demonstrates that the approach can reduce the size of both breast and brain tumors in laboratory experiments.
When cancer infiltrates the brain, treatment can become challenging, primarily due to the presence of the blood-brain barrier. This nearly impervious membrane acts as a barrier, separating the brain from the rest of the body.
According to Shanta Dhar, Ph.D., an Associate Professor of Biochemistry and Molecular Biology and Assistant Director of Technology and Innovation at Sylvester, who led the study, the Sylvester team's nanoparticle may one day be used to treat the metastases with the added benefit of treating the primary tumor at the same time.
In preclinical studies, the researchers demonstrated that their approach could reduce breast and brain tumors by loading the particle with two prodrugs that target the mitochondria, the cell's center for energy production.
When referring to commercially available COVID-19 vaccines, which use nanoparticles in their formulation, Shanta Dhar said, "I always say nanomedicine is the future, but of course we have already been in that future. Nanomedicine is definitely also the future for cancer therapeutics."
The novel approach combines two medications created in Dhar’s lab. It targets the energy sources of cancer with a nanoparticle composed of a biodegradable polymer, which the Dhar team previously created. Stifling the metabolism of cancer cells can be an efficient way to eradicate tumors without endangering healthy tissues, as they frequently have a different type of metabolism than healthy cells.
One of these medications is a modified form of the traditional chemotherapy drug cisplatin; it stops cancer cells from growing by causing damage to their DNA. However, tumor cells are capable of DNA repair, which can occasionally result in cisplatin resistance. Dhar's group altered the medication to target mitochondrial DNA rather than nuclear DNA, which is the DNA that makes up human chromosomes and the genome.
The energy sources for human cells are called mitochondria, which also have much smaller genomes of their own. However, mitochondria lack the DNA repair machinery found in the larger genomes for cancer treatment.
According to Dhar, creating a nanoparticle that can enter the brain is difficult. Throughout her independent career, she has been dedicated to researching nanoparticles. In a prior project examining various polymer forms, the researchers observed that a tiny portion of some of these nanoparticles made it to the brain in preclinical tests.
Dhar's group refined polymers to create a nanoparticle that could pass through the outer membrane of mitochondria and the blood-brain barrier.
There have been a lot of ups and downs to figuring this out, and we’re still working to understand the mechanism by which these particles cross the blood-brain barrier.
Shanta Dhar, Ph.D., Associate Professor and Study Lead, Department of Biochemistry and Molecular Biology, Sylvester Comprehensive Cancer Center
Subsequently, the team conducted preclinical studies to test the specialized drug-loaded nanoparticle and discovered that it effectively reduces breast tumors as well as breast cancer cells that were seeded into the brain to form tumors. In lab tests, the drug-nanoparticle combination considerably increased survival rates and seemed nontoxic.
The group's next goal is to closely mimic human brain metastases in the lab by testing their approach, maybe with patient-derived cancer cells. Additionally, they intend to test the medication in lab-created models of glioblastoma, an especially aggressive form of brain cancer.
I’m really interested in polymer chemistry, and using that toward medical purposes really fascinates me. It’s great to see that applied toward cancer therapeutics.
Akash Ashokan, Doctoral Student and Study Co-First Author, University of Miami Miller School of Medicine
Ashokan works along with doctoral student Shrita Sarkar.
Journal Reference:
Ashokan, A., et al. (2024) Simultaneous targeting of peripheral and brain tumors with a therapeutic nanoparticle to disrupt metabolic adaptability at both sites. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2318119121.