Engineers on the College of California San Diego have developed modular nanoparticles that may be simply personalized to focus on completely different organic entities akin to tumors, viruses or toxins. The floor of the nanoparticles is engineered to host any organic molecules of selection, making it attainable to tailor the nanoparticles for a big selection of purposes, starting from focused drug supply to neutralizing organic brokers.
Up to now, creating distinct nanoparticles for various organic targets required going via a unique artificial course of from begin to end every time. However with this new approach, the identical modular nanoparticle base might be simply modified to create an entire set of specialised nanoparticles.
“This can be a plug and play platform expertise that permits for speedy modification of a practical organic nanoparticle,” stated Liangfang Zhang, a professor of nanoengineering on the UC San Diego Jacobs Faculty of Engineering.
Zhang and his staff element their work in a paper, titled “A modular method to enhancing cell membrane-coated nanoparticle performance utilizing genetic engineering,” revealed Oct. 30 in Nature Nanotechnology.
The modular nanoparticles include biodegradable polymer cores coated with genetically modified cell membranes. The important thing to their modular design is a pair of artificial proteins, often known as SpyCatcher and SpyTag, which might be particularly designed to spontaneously—and completely—bind with one another. This pair is usually utilized in organic analysis to mix varied proteins.
On this research, Zhang and his staff harnessed the pair to create a system for attaching proteins of curiosity to a nanoparticle floor with ease.
Right here’s the way it works: SpyCatcher is embedded onto the nanoparticle floor, whereas SpyTag is chemically linked to a protein of curiosity, akin to one focusing on tumors or viruses. When SpyTag-linked proteins come into contact with SpyCatcher-decorated nanoparticles, they readily bind to one another, enabling proteins of curiosity to be effortlessly connected to the nanoparticle floor.
For instance, to focus on tumors, SpyTag might be linked to a protein designed to hunt out tumor cells, and that SpyTag-linked protein is then connected to the nanoparticle. If the goal shifts to a particular virus, the method is equally simple: merely hyperlink SpyTag to a protein focusing on the virus and fasten it to the nanoparticle floor.
“It’s a quite simple, streamlined and simple method to functionalizing nanoparticles for any organic utility,” stated Zhang.
To create the modular nanoparticles, the researchers first genetically engineered human embryonic kidney (HEK) 293 cells—a generally used cell line in organic analysis—to precise SpyCatcher proteins on their floor. The cell membranes have been then remoted, damaged into smaller items, and coated onto biodegradable polymer nanoparticles.
These nanoparticles have been subsequently blended with SpyTag-linked proteins. On this research, the researchers used two completely different proteins: one focusing on the epidermal development issue receptor (EGFR) and the opposite focusing on human epidermal development issue receptor 2 (HER2), each of that are prevalent on the floor of varied most cancers cells.
As a proof of idea, the researchers examined these nanoparticles in mice with ovarian tumors. The nanoparticles have been loaded with docetaxel, a chemotherapy medicine, and administered to mice by way of intravenous injection each three days for a complete of 4 injections. Therapy with these nanoparticles suppressed tumor development whereas bettering survival fee. Handled mice had median survival of 63 to 71 days, whereas the median survival of untreated mice was 24 to 29 days.
The researchers need to additional enhance the modular nanoparticle platform for focused drug supply.
Along with most cancers therapy, Zhang is worked up about different potential purposes of this expertise. “As a result of we’ve got a modular nanoparticle base, we will simply connect a neutralizing agent on the floor to neutralize viruses and organic toxins,” he stated.
“There’s additionally potential for creating vaccines by attaching an antigen on the nanoparticle floor utilizing this modular platform. This opens the door to a wide range of new therapeutic approaches.”
Extra info: A modular method to enhancing cell membrane-coated nanoparticle performance utilizing genetic engineering, Nature Nanotechnology (2023). DOI: 10.1038/s41565-023-01533-w