Getting cancer drugs to the correct locations is one of the biggest challenges in treating solid tumors, especially brain cancer. The brain is protected by the blood-brain barrier, which blocks more than 98 percent of drugs from reaching the tissue.
To address this obstacle, Natalie Artzi, PhD, a principal investigator in the Division of Bioengineering in Medicine, and her team are focused on engineering biomaterials that can enhance the effectiveness of drug delivery. They have produced a wide library of therapeutic nanoparticles, ranging from polymeric to metallic to lipid-based platforms. Her team also engineers materials to be tissue responsive, shifting from the concept of “one material fits all” to understanding and adapting material design to match disease pathology. Ultimately, her team is designing delivery mechanisms that can release on demand and more effectively to the right locations.
“One of the major challenges in the treatment of brain cancer is delivery,” said Artzi. “With our unique biomaterial approaches, we want to considerably increase drug delivery efficiency.”
Driven to Deliver
For Artzi, this battle is personal. One of her biggest motivations is a family friend whose son was diagnosed with brain cancer.
“Patients, especially young ones, are at the mercy of existing therapies,” she said. “When you see this firsthand and understand the need, and then recognize that you can make a difference, it doesn’t matter what it takes in terms of time and effort. You will make it happen. That is what drives what we do.”
Brain cancer is the leading cause of cancer-related deaths among children. In the last four decades, there has been little improvement in the survival of patients with brain cancer, with many dying 12 to 18 months after diagnosis. These drastic numbers emphasize the great need for better drug delivery to improve patient outcomes.
Support from the Brigham
Innovation often begins with a bold but untested idea. In 2019, Artzi applied and competed in the BRIght Futures Prize competition to fund an ambitious project to develop a new way to treat brain cancer. Artzi’s team had been developing nanoparticles that could house cancer drugs, and they envisioned that during surgery to remove a tumor, an adhesive material containing the nanoparticles could be sprayed into the resection cavity, creating a hydrogel patch. But this approach had never been used for drug delivery.
“In 2019, this delivery platform was just an idea,” said Artzi. “We were learning more and more about the biological mechanisms associated with the disease and why biomaterials might help realize the potential of emerging therapies, but we had no funding to make it a reality. Before you can apply for any large-scale external grant, you need to have convincing data.”
This is where support from the Brigham came into play. In November 2019, Artzi won the BRIght Futures Prize and its $100,000 award to help fund experiments that generated proof-of-concept data.
“This set the stage for us to apply for and receive future grants from outside of the Brigham,” said Artzi. Indeed, the team received additional funds from the MIT Deshpande Center to help generate a data package to bring this technology to patients.
The results were stunning. Artzi’s team successfully manufactured the adhesive hydrogel and showed not only accurate delivery, but also the ability to have sustained delivery over time. The latter is an especially key characteristic for effective drug treatment in the brain, which typically acts swiftly to clear foreign particles.
“Not only were we able to have better accumulation of the drug and better efficacy, but we were also able to eliminate a lot of the side effects that one sees when drugs are delivered in a non-targeted, non-specific manner to the bloodstream,” said Artzi. “What was an idea just a few years ago, has now matured to the point where we are working to translate this technology.”
The Brigham has financially supported her research as well as given her work exposure, and it has also provided her with an invaluable resource: an ecosystem of experts. Artzi credits collaborations within the Brigham for many of her successes, and has expressed her gratitude, for her colleagues’ mentorship, guidance and brainstorming on future directions.
One of those future directions that Artzi hopes to continue developing is based on a microneedle polymeric patch used to deliver drugs noninvasively and in a painless matter through the skin. The skin is the body’s largest organ and is specifically designed to keep out invaders. Microneedles are one way to circumnavigate this barrier and Artzi’s team aims to use them to deliver microparticles and help the immune system recognize cancer cells as well as to suppress the immune system in autoimmune skin diseases.
In 2019, Artzi happened to serve as a reviewer alongside another Brigham faculty member at a national review panel. Jamil Azzi, MD, an associate physician in the Renal Transplant Division, shared more just a last name initial with Artzi—as they began chatting, they realized their clinical and research interests overlapped. Artzi and Azzi realized that the microneedle hydrogel Artzi was developing might help manage the care of patients with skin diseases, such as alopecia areata—an autoimmune disease in which patients lose all their hair—and patients receiving skin grafts.
Together with the Azzi lab, Artzi’s team validated the patch in preventing skin allograft rejection by the delivery of factors that can attract and locally expand T-regulatory cells at the allograft site. The team is now leveraging their technology to alopecia areata by promoting local immune regulation.
Artzi attributes their success in part to Brigham Ignite, which has helped to support and fund their idea. This year, Artzi and Azzi were among the first Brigham Ignite Award recipients, and will receive funding as well as guidance on licensing, product development, intellectual property, and commercialization. Now, Artzi and Azzi are working diligently to bring their innovation closer to the clinic.
“With all of the resources that the Brigham provides to its researchers and teams, there is no better time than now to make a difference for our patients,” said Artzi. “We all have a passion to help advance human health by using instrumental tools to improve drug delivery and fostering cutting-edge therapies.”