Engineers on the College of California San Diego have developed modular nanoparticles that may be simply custom-made to focus on completely different organic entities comparable to tumors, viruses or toxins. The floor of the nanoparticles is engineered to host any organic molecules of selection, making it doable to tailor the nanoparticles for a big selection of functions, starting from focused drug supply to neutralizing organic brokers.
Up to now, creating distinct nanoparticles for various organic targets required going by a distinct artificial course of from begin to end every time. However with this new approach, the identical modular nanoparticle base may be simply modified to create a complete set of specialised nanoparticles.
“It is a plug and play platform know-how that enables for fast modification of a practical organic nanoparticle,” mentioned Liangfang Zhang, a professor of nanoengineering on the UC San Diego Jacobs Faculty of Engineering.
Zhang and his group element their work in a paper, titled “A modular strategy to enhancing cell membrane-coated nanoparticle performance utilizing genetic engineering,” printed Oct. 30 in Nature Nanotechnology.
The modular nanoparticles encompass 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 can be particularly designed to spontaneously—and completely—bind with one another. This pair is often utilized in organic analysis to mix numerous proteins.
On this research, Zhang and his group 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, comparable 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 hooked up to the nanoparticle floor.
For instance, to focus on tumors, SpyTag may be linked to a protein designed to hunt out tumor cells, and that SpyTag-linked protein is then hooked up to the nanoparticle. If the goal shifts to a selected virus, the method is equally easy: merely hyperlink SpyTag to a protein focusing on the virus and fasten it to the nanoparticle floor.
“It’s a quite simple, streamlined and easy strategy to functionalizing nanoparticles for any organic utility,” mentioned 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 specific 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 assorted 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. Remedy with these nanoparticles suppressed tumor development whereas bettering survival charge. 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 happy about different potential functions of this know-how. “As a result of we’ve a modular nanoparticle base, we will simply connect a neutralizing agent on the floor to neutralize viruses and organic toxins,” he mentioned.
“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 data: A modular strategy to enhancing cell membrane-coated nanoparticle performance utilizing genetic engineering, Nature Nanotechnology (2023). DOI: 10.1038/s41565-023-01533-w