A small shift in temperature is enough to make a new class of nanoparticles snap together, offering a novel way to deliver fragile medicines.
Researchers at the University of Chicago Pritzker School of Molecular Engineering (UChicago PME) have engineered these polymer-based nanoparticles that self-assemble at room-temperature in water—no harsh chemicals, specialized equipment or processing required.
Described in Nature Biomedical Engineering, the new nanoparticles form under conditions gentle enough to deliver proteins, which are unstable in the current version of this technology. This discovery could broaden access to next-generation biologics 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.”
From problem to platform
Nanoparticles are key to protecting delicate drugs like RNA and proteins from being degraded in the body before they reach the right cells.
For example, lipid nanoparticles made of fatty molecules enabled the COVID-19 mRNA vaccines. But this kind of nanoparticle relies on alcohol-based solvents and sensitive manufacturing steps—making them hard to scale and poorly suited 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 at the time of the research. “We also wanted to make it scalable, without needing toxic solvents or complicated microfluidics.”
Hossainy hypothesized that polymer-based nanoparticles could offer a more robust, customizable alternative. He outlined the required characteristics—the immune system will only respond to particles with certain shapes, sizes and charges.
He then used chemical tools to begin designing new nanoparticles from scratch.
After trying and fine-tuning more than a dozen different materials, he found one that worked. In cold water, the polymer—and any desired protein—remained dissolved. But when heated to room temperature, the polymer self-assembled into uniformly sized nanoparticles surrounding the protein molecules.
“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.”
Carrying versatile cargo
To test the new nanoparticles, Hossainy worked with colleagues in Rowan’s lab as well as with former UChicago PME Prof. Jeffrey Hubbell, now at New York University. They first showed the particles can encapsulate protein and RNA cargo in much higher levels than most current systems and can be freeze-dried and stored without refrigeration until needed.
In the context of vaccination, Hossainy and his collaborators found the nanoparticles could effectively carry a protein and, when injected into mice, lead the animals’ immune systems to generate long-lasting antibodies against that protein. Another experiment showed the nanoparticles could also carry proteins designed to prevent an immune response in the context of allergic asthma. And a third showed that injecting the nanoparticles into tumors could block cancer-related genes and suppress 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.”
A scalable solution for worldwide vaccines
One of the biggest advantages of the new polymer-based nanoparticles over current lipid-based models is the potential for low-tech, decentralized production. Hossainy says he imagines being able to ship freeze-dried formulations of the nanoparticles to anywhere in the world.
When they need to be used, they can be mixed in cold water, warmed up and will be ready to deliver to patients.
“Being able to store these dry drastically improves the stability of the RNA or protein,” said Hossainy.
The group is continuing to work on fine-turning the particles to carry more types of cargo, including messenger RNA like that used in the COVID-19 vaccines. They also plan to collaborate on pre-clinical trials to apply the particles to real-world vaccine or drug delivery challenges.
The researchers are working with the Polsky Center for Entrepreneurship and Innovation to commercialize the technology.
Citation: “Thermoreversibly Assembled Polymersomes for Highly Efficient Loading, Processing, and Delivery of Protein and siRNA Biologics,” Hossainy et al, Nature Biomedical Engineering, August 6, 2025. DOI: 10.1038/s41551-025-01469-7
Funding: This work was supported by the National Institute of Allergy and Infectious Diseases (75N93019C00041) and the Chicago Immunoengineering Innovation Center.
This article was originally published on the UChicago PME website.
