NORTHWESTERN (US)—Gene therapy holds promise in treating a myriad of diseases, including cancer, heart disease, and diabetes. Developing a scalable system for delivering genes to cells both efficiently and safely, however, has been a challenge.
Now a team of Northwestern University researchers has introduced the power of nanodiamonds as a novel gene delivery technology that combines key properties in one approach: enhanced delivery efficiency along with outstanding biocompatibility.
“Finding a more efficient and biocompatible method for gene delivery than is currently available is a major challenge in medicine,” says Dean Ho, who led the research. “By harnessing the innate advantages of nanodiamonds, we now have demonstrated their promise for gene therapy.”
Ho is an assistant professor of biomedical engineering and mechanical engineering in the McCormick School of Engineering and Applied Science and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
Ho and his research team engineered surface-modified nanodiamond particles that successfully and efficiently delivered DNA into mammalian cells. The delivery efficiency was 70 times greater than that of a conventional standard for gene delivery. The new hybrid material could impact many facets of nanomedicine.
“A low molecular weight polymer called polyethyleneimine-800 (PEI800) currently is a commercial approach for DNA delivery,” says Xue-Qing Zhang, a postdoctoral researcher in Ho’s group and the paper’s first author. “It has good biocompatibility but unfortunately is not very efficient at delivery. Forms of high molecular weight PEI have desirable high DNA delivery efficiencies, but they are very toxic to cells.”
Multiple barriers confront conventional approaches, making it difficult to integrate both high-efficiency delivery and biocompatibility into one gene delivery system. But the Northwestern researchers were able to do just that by functionalizing the nanodiamond surface with PEI800.
The combination of PEI800 and nanodiamonds produced a 70 times enhancement in delivery efficiency over PEI800 alone, and the biocompatibility of PEI800 was preserved. The process is highly scalable, which holds promise for translational capability.
Ho and his research team originally demonstrated the application of nanodiamonds for chemotherapeutic delivery and subsequently discovered that the nanodiamonds also are extremely effective at delivering therapeutic proteins. Their work further has shown that nanodiamonds can sustain delivery while enhancing their specificity as well.
Having demonstrated the safety of nanodiamonds and their applicability toward a variety of biological uses, Ho’s team is pursuing aggressively the steps necessary to push them towards clinical relevance. Current studies are boosting the targeting capabilities of the nanodiamonds while also evaluating their pre-clinical efficiency.
“There’s a long road ahead before the technology is ready for clinical use,” Ho says, “but we are very pleased with the exciting properties and potential of the nanodiamond platform.”
The National Science Foundation, the Wallace H. Coulter Foundation and the V Foundation for Cancer Research supported the research. The results are published online by the journal ACS Nano. Researchers from Northwestern and Eiji Osawa, from the NanoCarbon Research Institute at Shinshu University, Nagano, Japan, contributed to the report.
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