University of Wisconsin-Madison engineers have developed a nanoparticle that could safely carry a variety of payloads into targeted cells, giving researchers a versatile, nonviral option for delivering drugs, gene-editing tools, DNA and more.
Shaoqin Sarah Gong, a Vilas Distinguished Professor of biomedical engineering and faculty member at the Wisconsin Institute for Discovery, and collaborators across the UW-Madison campus have detailed their work in a paper that’s published online and slated to appear in the August 2020 issue of the Journal of Controlled Release.
The group created a hybrid nanoparticle that features a silica-metal-organic framework—built within a water droplet—that allows it to transport a range of cargoes that mix with water. By customizing the surface of the nanoparticle, researchers can target specific cell types. And because the nanoparticle is pH-responsive, it won’t release its contents until it’s taken up by a cell.
In general, nanoparticles offer greater safety than viral vectors—the usual means of delivery for gene therapies—which can trigger immune responses.
“Nonviral nanodelivery systems are overall safer than the viral-based delivery systems, but they might be less efficient, because viral vectors get into the cells easily and do their job,” says Yuyuan Wang, the paper’s first author and a postdoctoral researcher in Gong’s lab. “So we’re trying to design and develop biocompatible nonviral nanoparticles that have enhanced efficiency. It’s a challenging job, but we are able to continuously improve the nanodelivery systems.”
The researchers demonstrated their nanoparticle’s effectiveness by delivering the anticancer drug doxorubicin hydrochloride, DNA and messenger RNA, and the popular genome-editing tool CRISPR-Cas9 in a variety of cell types.
Collaborator Bikash Pattnaik, an associate professor of pediatrics at UW-Madison, also tested the nanoparticle by injecting it below the retinas of mice and successfully editing genomes in retinal pigment epithelium (RPE) cells, which support the eye’s photoreceptors. Genetic abnormalities in the RPE cells are implicated in a number of eye diseases.
“We can deliver CRISPR-Cas9-based genome editing machinery into these RPE cells and then change the genome. This may help to alleviate the symptoms of the patients suffering from RPE genetic disorders,” says Gong, who acknowledges many steps remain in developing such a therapy.
Gong’s lab is pursuing a new method to create even smaller nanoparticles (the current one measures 110 nanometers in diameter) that work more efficiently. She and her lab members are also exploring potential applications for systemic diseases.
Gong is also a faculty member of the Carbone Cancer Center and the McPherson Eye Research Institute.
College of Engineering faculty members Krishanu Saha (associate professor of biomedical engineering) and Zhenqiang “Jack” Ma (Lynn H. Matthias Professor in Engineering and Vilas Distinguished Achievement Professor of electrical and computer engineering) were also authors on the paper.
Author: Tom Ziemer