Nanoparticles improve exosome therapeutic manufacturing
Original story from Xi’an Jiaotong-Liverpool University (Suzhou, China).
A new method uses nanoparticles to a major manufacturing challenge that has slowed the development of exosome-based therapeutics.
Researchers from Xi’an Jiaotong-Liverpool University have developed a streamlined process that makes it easier to produce exosomes. Using a nanoparticle-based system, the researchers were able to overcome a major barrier that has slowed the medical and industrial deployment of these therapies.
Exosomes are naturally released by cells and carry signals that can help repair tissues or regulate the immune system. Exosomes do not divide or mutate over time, which makes them safer than living cell therapies and less likely to cause side effects such as tumor growth. Scientists can also engineer exosomes, designing enhanced versions that are even more effective for treatment.
“The field of cell therapy is really starting to change medicine,” explains Gang Ruan of Xi’an Jiaotong-Liverpool University’s Wisdom Lake Academy of Pharmacy, who led the study. “We have seen successes with stem cells repairing damaged tissues and immune cells fighting cancer. An engineered exosome is like a supercharged version of a natural exosome. You can think of it like Iron Man or Captain America – enhanced versions of humans after engineering.”
Despite their promise, engineered exosomes are difficult to produce efficiently because the process involves multiple steps: cells must first release the exosomes, therapeutic substances like drugs must be loaded into them, the exosomes must be separated from the liquid they were grown in, and finally, they need to be stored so they remain stable. Many existing technologies improve only one or two of these steps, which makes production slow, expensive and hard to scale.
To overcome this challenge, the team developed a platform centered on a specially designed nanoparticle. When mesenchymal stem cells are grown with these nanoparticles, the cells release far more exosomes than usual, and drugs and magnetic particles are automatically packed into the exosomes as they form.
“We created a manufacturing system that improves all four steps at once,” says Xiaowei Wen of Xi’an Jiaotong-Liverpool University’s Jiangsu Province Higher Education Key Laboratory of Cell Therapy Nanoformulation, a co-first author of the study. “It works because we combined three new ideas: a new interaction between nanoparticles and cells, a new type of nanomaterial, and a new design for the manufacturing equipment. This is the first time the entire process has been integrated in this way.”
The exosomes are isolated using a new magnetic technique called mobile internal magnetic separation (MIMS). Unlike traditional methods, which slow down as production scale increases, MIMS allows exosomes to be collected quickly and efficiently even at large scales. The engineered exosomes also remain stable during storage, keeping their structure intact even after freeze-drying and later rehydration.
The product has a special “Russian doll”-like structure, that is, drug-in-nanoparticle-in-exosome. The special structure gives it the power to hold an extraordinarily large amount of drug molecules in each exosome without damaging the exosome stability. The nanoparticle in the exosome also enables imaging and tracking in a biological environment, which has been difficult for exosomes in the past.
The researchers tested the technology in models of Parkinson’s disease, pulmonary fibrosis, wound healing, heart failure, and polycystic ovary syndrome. “We found that this approach works across multiple diseases,” says Dr Ruan, who is also the director of the above-mentioned Jiangsu Key Laboratory of Cell Therapy Nanoformulation. “It’s not only practical and scalable but also maintains consistent quality, which is essential for industrial use, and could help patients gain faster access to safer and more effective engineered exosome therapies.”
He concludes: “It took years of cross-field teamwork in the Jiangsu key lab to bring this project to life. And the collaborations with our clinical partners, including the Fourth Affiliated Hospital of Soochow University and the Seventh Affiliated Hospital of Southern Medical University, were instrumental too.”