In a discovery that could expand access to new generation medicines and organic vaccines, researchers from the Molecular Engineering School at the University of Chicago Pritzker (Uchicago PME) have nanoparticles based on designed polymer that are formed with a simple temperature change – rigorous products, no specialized equipment and no necessary treatment.
The new nanoparticles, described in Biomedical engineering of natureAmbient temperature self-assembly in water and, due to these soft conditions, can provide proteins, which are unstable in many existing nanoparticles formulations.
What excites me in this platform is its simplicity and versatility. By simply warming a sample of the temperature of the refrigerator at room temperature, we can reliably make nanoparticles ready to deliver a wide variety of organic drugs. “”
Stuart Rowan, co-ennior author, Professor Barry L. Maclean for innovation and the molecular engineering company in Uchicago Pritzker Engineering and scientist of the Argonne National Laboratory staff
From the problem to the platform
Nanoparticles are essential to protect delicate drugs such as RNA and proteins from degradation in the body before reaching good cells. The lipid nanoparticles (LNP), in oily molecules, allowed COVVI-19 mRNA vaccines, for example. But LNP rely on alcohol solvents and sensitive manufacturing stages making them poorly adapted to the delivery of proteins and on a difficult scale.
“We wanted to make a delivery system that could work for RNA therapies and therapies at present, most platforms specialize for only one,” said the first author Samir Hossainy, a student graduated from Uchicago PME. “We also wanted to make it evolving, without the need for toxic solvents or complex microfluidics. »»
Hossainy hypothesized that nanoparticles based on polymer could offer a more robust and customizable alternative. He described the required characteristics; The immune system will only respond to particles with certain sizes, forms and charges. Then he used chemical tools to start designing new nanoparticles from zero.
After trying and refined, more than a dozen different materials, he found one that worked. In cold water, polymer – and everything that is done by desired protein has dissolved. But when heated at room temperature, the polymer has self-assembled in nanoparticles of uniform (or “polymers”) surrounding the protein molecules.
“Our size of particles and our morphology are only dictated by the chemistry of the polymers that I designed from bottom to top,” explained Hostainy. “We don’t have to worry about the formation of different particles, which is a challenge with many nanoparticles today. »»
Versatile cargo transport
To test the new polymers, Hossainy worked with colleagues from the Rowan laboratory as well as with the former Uchicago SME, Professor Jeffrey Hubbell, now at New York University. First, they have shown that particles can encapsulate more than 75% of proteins and almost 100% of the short interference cargo (SIRNA) higher than most current systems and that they can be dried and stored without refrigeration until they are necessary.
In the context of vaccination, Stalsainy and his collaborators have found that polymers could effectively transport a protein and, when injected into mice, lead the immune systems of animals to generate lasting antibodies against this protein. Another experience has shown that nanoparticles could also transport proteins designed to prevent an immune response in the context of allergic asthma. And a third has shown that the injection of polymers into tumors could block cancer genes and remove tumor growth in mice.
“What is exciting is that we did not need to adapt a different system for each use case,” said Houssainy. “This formulation has worked for everything we have tried proteins, RNA, immune activation, immune deletion and direct targeting of tumors. »»
An evolutionary solution for global vaccines
One of the largest advantages of new polymers compared to current LNPs is the decentralized low -technology production potential. Hossainy says he imagines being able to send lyophilized formulations of nanoparticles to all over the world. When they should be used, they can be mixed in cold water, reheated and will be ready to deliver to patients.
“The possibility of storing these secs considerably improves the stability of RNA or protein,” said Houssainy.
The group continues to work on the end of the particles to transport more types of freight, including messenger RNA like that used in COVVI-19 vaccines (generally much larger than the Arnsi used in the current trial). They also plan to collaborate on preclinical trials to apply polymers to the challenges of the vaccine or the administration of real drugs.