Delivering medication precisely where the body needs it is one of nanomedicine’s biggest challenges. Kuei-Chun (Mark) Wang has been working to overcome that obstacle by designing nanosized drug carriers capable of moving through the body and accumulating in diseased tissues. This work has earned him a prestigious National Science Foundation Faculty Early Career Development Program (CAREER) Award.
Inflammation in the brain’s blood vessels plays an important role in the progression of many neurological conditions. Wang, an assistant professor in the School of Biological and Health Systems Engineering, part of the Ira A. Fulton Schools of Engineering at Arizona State University, is engineering biomimetic nanoparticles that selectively interact with these inflamed blood vessels in the brain, enabling more precise delivery of medical imaging and therapeutic agents.
“We are engineering the nanoparticles to control how they behave in real physiological environments and how to precisely control their interactions with inflamed vascular tissues in the body,” says Wang. “Our objective is to understand how we can send medicine specifically to regions of inflammation. Many treatments fail not because the drugs themselves are ineffective, but because they cannot reach the right places in the body.”
Rather than relying solely on synthetic materials to guide treatments to the right spots, Wang’s team incorporates biological features derived from natural cell membranes into engineered nanoparticles. The goal is to enable precise control over how these nanoparticles move through the body and where they accumulate after administration.
“More specifically, these nanoparticles are engineered with white blood cell-like surface features and small targeting molecules that help guide them to circulate effectively and selectively target inflamed blood vessels,” Wang says.
By leveraging native vascular recognition mechanisms, these biomimetic designs improve targeting precision while minimizing unintended interactions in circulation. The project will help reveal how engineered nanomaterials behave in complex inflammatory environments and establish design principles for biomimetic nanocarriers.
More broadly, Wang’s research addresses the urgent need for more effective treatment for cerebrovascular and neurological disorders that affect hundreds of millions of people worldwide.
Navigating biologically complex processes
Accomplishing this work of integrating insights from biology and materials design requires understanding how nanoparticles behave inside the body and carefully studying them in complex biological environments.
“We want to develop a deep understanding of how these nanoparticles behave in real physiological environments,” says Wang, who is also affiliated with ASU’s John Shufeldt School of Medicine and Medical Engineering. “That includes how they interact with circulating proteins, blood flow and the vascular wall itself. With that knowledge, we can begin to design nanomedicine that targets diseased tissues more precisely.”
To do that, Wang’s lab has developed an experimental framework to examine nanoparticle behavior in complex vascular environments. The research team will first use highly sensitive molecular binding measurements to quantify how their nanoparticles bind with marker proteins present in the diseased blood vessels.
Next, the researchers test the engineered particles in three-dimensional human microvascular models grown on bioengineered chips that replicate realistic vascular environments. These platforms allow researchers to evaluate nanoparticle behavior before advancing to more complex biological studies.
“We use human microvasculature-on-a-chip models to understand how nanoparticles transport and bind diseased blood vessels in controlled environments,” Wang says of the work being done in his lab in collaboration with Mehdi Nikkhah, a professor in the School of Biological and Health Systems Engineering. “We then examine how well the biomimetic design principles translate in vivo. This creates a pathway from fundamental nanoparticle design and formulation to preclinical testing.”
Broadening possibilities for treating complex diseases
If successful, the research could significantly expand engineers’ abilities to design biologically inspired nanotherapeutics, says Heather Clark, director of the School of Biological and Health Systems Engineering and senior associate dean in the John Shufeldt School of Medicine and Medical Engineering.
“By integrating a mechanism-driven framework with cutting-edge biomimicry to control nanoscale transport across neurovascular interfaces, together with a powerful educational vision,” Clark says, “this work is poised to redefine targeted treatment strategies for neuroinflammatory disorders while also training a new generation in bioengineering at the intersection of nanotechnology and precision medicine.”
Wang’s work will also provide hands-on research training for undergraduate and doctoral students while introducing emerging nanomedicine concepts into bioengineering education. He says the project will also support expanded digital course content and educational outreach efforts to promote science literacy beyond the classroom.
