Tuning Cancer Therapy with Acoustic Drug Delivery

As a child, Carolyn Schutt Ibsen, a biomedical engineer at Oregon Health and Science University (OHSU), enjoyed taking things apart to see how they worked. “I have always found it really exciting and fulfilling to be able to build things as well,” she said. As she considered her options for graduate research, Schutt Ibsen reflected on her family members’ journey through cancer treatments and its impact on their quality of life, and she decided to apply her engineering skills to the outstanding challenge of improving cancer therapy. “That kind of checked all the boxes for me in terms of thinking what would be a really fulfilling career path,” she said. This drew Schutt Ibsen to studying novel drug delivery mechanisms with Sadik Esener, a biomedical engineer, at the University of California, San Diego for her PhD in bioengineering. Today, she combines her interdisciplinary research with her passion for research training to help advance the future of cancer therapy.

Tackling Cancer Using Ultrasound

In Esener’s group, Schutt Ibsen first approached interventions to improve cancer therapy through nanomedicine. Esener’s team sought to use ultrasound to manipulate nanosized, gas-filled bubbles that would respond to this form of energy as a noninvasive therapy.¹ “That was the most exciting thing I’d ever heard,” Schutt Ibsen recalled.

In this approach, researchers load these microscopic bubbles with their intervention and introduce them into either cell or animal models. These bubbles remain stable until scientists apply an ultrasound frequency, at which point they rupture.² Local shockwaves and water jets produced from these ruptured bubbles can disrupt cell membranes, allowing the drug or gene to enter the cell.³

Working alongside biologists and engineers, Schutt Ibsen mastered encapsulating DNA and the microbubble in a liposome and delivering these to target cells using ultrasound.⁴ She also investigated the influence of lipid composition and the distance between microbubbles on these vehicles and their response to ultrasound energy, aiming to improve their therapeutic application.^5,6

As she approached the end of her PhD, Schutt Ibsen wanted to apply this ultrasound approach in tissue engineering and 3D models. “I started to integrate these ideas together,” Schutt Ibsen said. “Can we create new 3D materials for tissue engineering and build actual tissue structures that can be remote controlled with ultrasound energy?”

One group in particular caught her attention: Molly Stevens, a bioengineer at Imperial College London, and her team studied biomaterials and built such tissue models. “I had always been impressed by the incredible work being done in [Stevens’s] group and just how interdisciplinary the science was [that] was going on in her group,” Schutt Ibsen said.

“I thought she was really thoughtful, clearly a very good scientist,” said Stevens, who now leads a group at University of Oxford, about her first impression of Schutt Ibsen. “She also brought a new skill set to the lab that we weren’t currently working on, and that was very exciting.”

In her new position, Schutt Ibsen set up the ultrasound system that the group began using to incorporate energy-responsive materials into their projects. Drawing on her expertise in ultrasound systems and vehicle design and applying Stevens’s optimized tissue engineering techniques, she designed ultrasound-responsive hydrogel materials for applications in tissue engineering.⁷

Schut Ibsen recalled that the breadth of Stevens’s research projects from nanoscale materials to tissue models and her inspiring leadership style shaped her own approach as a group leader. “The way that she fostered communication between different scientists with the different backgrounds, and also supported the development of all those people, while also being very kind, are things that I appreciated.”

I think we’ve just scratched the surface of what we can do with these ultrasound responsive biomaterials.

—Carolyn Schutt Ibsen, Oregon Health and Science University

An Ink at the Intersection of Tissue Engineering and Ultrasound Delivery

In 2018, Schutt Ibsen started her own research lab at OHSU, where she applies tissue engineering and energy-responsive materials toward developing tumor models and improving drug delivery. “She’s working in a really interesting area, because there aren’t that many people that are looking at the interface of ultrasound and biomedical systems in quite the same approach that she’s taking,” Stevens said.

A cornerstone of Schutt Ibsen’s research approach is centering interdisciplinary research. “There’s really exciting things that can happen when engineers talk to biologists or when material scientists talk to people in engineering fields,” she said.

For example, Schutt Ibsen’s group incorporated bioprinting methods that she learned from Stevens’s group with energy-responsive materials in drug delivery. While bioprinting can replicate many complex structures, Schutt Ibsen explained that researchers still don’t have control of what cells are doing or when they are doing things. She and her team developed a novel bioink that responded to ultrasound so that the researchers could control where their cargo delivered a gene within a 3D construct.⁸ The bioink has applications for gene therapy in cancer as well as regenerative medicine.

In 2024, the Biomedical Engineering Society’s Cellular and Molecular Biology group named Schutt Ibsen a 2024 Young Innovator in cellular and molecular bioengineering as part of her work on energy-responsive bioink. She also received the Rising Star Junior Faculty Award from the same group the previous year.

“It’s been nice to see her be recognized and be acknowledged for all the cool work that she’s doing,” said Lesley Chow, a materials engineer at Lehigh University. Chow, who also worked in Stevens’s lab but did not overlap with Schutt Ibsen, met the latter at a conference. “There was just an immediate kinship,” Chow said. “[Since then] we just kept crossing paths and making sure that anytime we’re at the same conference or meeting, we connect with each other.”

New Methods for Modeling and Targeting Cancer

Beyond drug delivery, Schutt Ibsen and her team are also interested in studying the early stages of cancer development. Connections with clinicians who see cancer patients help the researchers better model real tumors and their unique architecture.

“It’s challenging to be able to understand the early stage of these diseases, because often patients don’t come in until their cancer has progressed significantly further,” Schutt Ibsen said. To address this gap, Schutt Ibsen is developing models of precancerous tissues. The team intends to use their energy-responsive and gene delivery methods to stimulate oncogenesis in individual cells. These models will allow them to observe how the cells’ 3D environment influences tumor development.

“What I think is really cool about that is that it could really lead us to understanding more about how cancer starts, and let us identify ways to intervene earlier,” Chow said. In her research, Chow synthesizes biomaterials for tissue engineering and regenerative medicine. She explained that she was used to seeing light or mechanical stimulation used, and that Schutt Ibsen’s work was her first exposure to ultrasound as a stimulus method in bioengineering, which she added has been interesting to see become more popular in bioengineering research.

“I think we’ve just scratched the surface of what we can do with these ultrasound-responsive biomaterials,” Schutt Ibsen said. For example, her group is currently exploring ways to incorporate sensors in the structures that report conditions of the cell environment. Another area that Schutt Ibsen sees on the horizon is the ability to create a library of energy-responsive materials. “There’s a lot of opportunities to multiplex this technology,” she said. This, she added, could allow researchers to induce patterns of gene expression within a tissue or at different locations.

“Her contribution is really very exciting and original,” said Nick Evans, a cell biologist studying regenerative medicine and drug delivery at the University of Southampton. Evans recently met Schutt Ibsen at the tissue engineering regenerative medicine international society.

Advancing Science Through Mentorship and Innovation

As early as graduate school, Schutt Ibsen was interested in mentoring new scientists, and continued mentoring trainees through her postdoctoral position. “The students really enjoyed working with her,” said Stevens. This interest drove her decision to become a principal investigator. “I try to foster an environment of that, where we all get to be excited about the science together,” she said.

“She’s a very collaborative, friendly, considerate, intelligent person,” Evans said. He added that Schutt Ibsen has gladly provided advice to him and his PhD student on aspects of their project involving ultrasound. “It’s my pleasure to know her.”

Amidst her recent accolades, though, Schutt Ibsen places training her students as her crowning achievement. “In the time that I’ve had my group so far, one of the most exciting and rewarding things is watching my students develop,” she said. “Some of the greatest moments that I have as a PI is when my students come to me and they’re like, ‘I got it to work.’ That’s always really exciting, or whenever they want to show me new results or data, I love that.”