Researchers at the University of Chicago Pritzker School of Molecular Engineering have developed a new class of polymer-based nanoparticles that self-assemble at room temperature in water. This method does not require harsh chemicals, specialized equipment, or complex processing.
The research, published in Nature Biomedical Engineering, describes how these nanoparticles form under gentle conditions suitable for delivering proteins, which are typically unstable with current nanoparticle technologies. The findings could expand the possibilities for delivering biologic drugs and vaccines.
“What excites me about this platform is its simplicity and versatility,” said co-senior author Stuart Rowan, the Barry L. MacLean Professor for Molecular Engineering Innovation and Enterprise at UChicago PME and a staff scientist at Argonne National Laboratory.
“By simply warming a sample from fridge temperature to room temperature, we can reliably make nanoparticles that are ready to deliver a wide variety of biological drugs.”
Nanoparticles play an important role in protecting sensitive drugs like RNA and proteins from being broken down before reaching their target cells. Lipid nanoparticles were key to the COVID-19 mRNA vaccines but depend on alcohol-based solvents and sensitive manufacturing steps, making them difficult to scale up and less suitable for protein delivery.
“We wanted to make a delivery system that could work for both RNA and protein therapies—because right now, most platforms are specialized for just one,” said first author Samir Hossainy, who was a UChicago PME graduate student during the research. “We also wanted to make it scalable, without needing toxic solvents or complicated microfluidics.”
Hossainy proposed that polymer-based nanoparticles could be more robust and customizable than existing options. He identified the necessary features so that particles would have the right shapes, sizes, and charges needed by the immune system.
He then used chemical techniques to design new nanoparticles from scratch. After testing more than twelve materials, he found one where the polymer—and any desired protein—remained dissolved in cold water but self-assembled into uniformly sized nanoparticles when warmed to room temperature.
“Our particle size and morphology is dictated only by the chemistry of the polymers that I designed from the bottom up,” explained Hossainy. “We don’t have to worry about different particle sizes forming, which is a challenge with a lot of today’s nanoparticles.”
To test their approach, Hossainy worked with colleagues in Rowan’s lab as well as former UChicago PME professor Jeffrey Hubbell (now at New York University). They showed that these particles can encapsulate protein and RNA cargo at higher levels than most current systems. The particles can also be freeze-dried and stored without refrigeration until needed.
In experiments related to vaccination, they found that injecting mice with these nanoparticles carrying a protein led to long-lasting antibody responses. Another experiment demonstrated their use in carrying proteins meant to prevent immune reactions in allergic asthma models. A third experiment showed injection into tumors could block cancer-related genes and slow tumor growth in mice.
“The exciting thing is that we didn't need to tailor a different system for each use case,” said Hossainy. “This one formulation worked for everything we tried—proteins, RNA, immune activation, immune suppression and direct tumor targeting.”
One major advantage over lipid-based models is potential ease of production worldwide: freeze-dried formulations could be shipped anywhere; mixing with cold water followed by warming would prepare them for patient use.
“Being able to store these dry drastically improves the stability of the RNA or protein,” said Hossainy.
The team plans further work on expanding cargo types—including messenger RNA—and aims to collaborate on pre-clinical trials applying this technology to vaccine or drug delivery challenges.
The study was supported by funding from the National Institute of Allergy and Infectious Diseases (75N93019C00041) and the Chicago Immunoengineering Innovation Center.