Nanoparticles Give Gene-Altering Lotion Power to Fight Cancer, Skin Disease

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A new application of nanoparticles is getting under people’s skin … in a good way.

Six years ago, researchers in the lab of Chad Mirkin, PhD, professor of chemistry, discovered that spherical nucleic acid (SNA) nanoparticles can enter cells and be used to effect gene regulation. The publication in Science later that year became the basis for multiple studies investigating their potential as therapy. That’s when Amy Paller, MD, chair of dermatology, entered the picture.

“I encouraged Dr. Mirkin to adapt his research to skin application and he was awarded a pilot study from our Northwestern Skin Disease Research Center (NU-SDRC) to jumpstart the testing,” said Paller, Walter J. Hamlin Professor of Dermatology and director of the NU-SDRC. “Through extensive collaboration during the past two years, lab members from his team and mine have performed various studies with encouraging results.”

Preliminary findings led to multiple National Institutes of Health (NIH) grants, in which the pair are co-investigators, and the recent publication online by Proceedings of the National Academy of Sciences.

 Amy Paller, MD, chair of dermatology

Unveiling the benefits of gene suppressive nanotherapy for treating skin disorders, the research goes beyond  any previously published material on the use of topically applied small interfering RNAs (siRNAs) in a commercial moisturizer.

The topical delivery of gene regulation technology to cells deep in the skin is extremely difficult because of the formidable defenses skin provides for the body. The Northwestern approach takes advantage of drugs consisting of novel spherical arrangements of nucleic acids. These structures, each about 1,000 times smaller than the diameter of a human hair, have the unique ability to recruit and bind to natural proteins that allow them to traverse the skin and enter cells.

Early targets of the novel treatment are melanoma and squamous cell carcinoma (two of the most common types of skin cancer), the common inflammatory skin disorder psoriasis, diabetic wound healing, and epidermolytic ichthyosis, a rare genetic skin disorder that has no effective treatment. Other targets could even include wrinkles.

Chad Mirkin, PhD, professor of chemistry

“The technology developed in the Mirkin lab is incredibly exciting because it can break through the skin barrier. This allows us to treat a skin problem precisely where it is manifesting – on the skin,” Paller said. “We can target our therapy to the drivers of disease, at a level so minute that it can distinguish mutant genes from normal genes. Risks are minimized, and side effects have not been seen to date in our human skin and mouse models.”

Mirkin developed the nanostructure platform used in this study in 1996, and the FDA-cleared technology is now the basis of powerful commercialized medical diagnostic tools. This collaborative research, however, is the first realization that the nanostructures naturally enter skin and that they can deliver a large payload of therapeutics.

“The field of medicine needs new constructs and strategies for treating disease,” said Mirkin, George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and director of Northwestern’s International Institute for Nanotechnology. “Many of the ways we treat disease are based on old methods and materials. Nanotechnology offers the ability to very rapidly create new structures with properties that are very different from conventional forms of matter. This collaborative study is a case in point.”

The key is the nanostructure’s spherical shape and nucleic acid density. Normal (linear) nucleic acids cannot get into cells, but these spherical nucleic acids can. SiRNA surrounds a gold nanoparticle like a shell; the nucleic acids are highly oriented, densely packed and form a tiny sphere. The RNA’s sequence is programmed to target the disease-causing gene.

“We now can go after a whole new set of diseases,” Mirkin said. “Thanks to the Human Genome Project and all of the genomics research over the last two decades, we have an enormous number of known targets. And we can use the same tool for each, the spherical nucleic acid. We simply change the sequence to match the target gene. That’s the power of gene regulation technology.”

“This all happened because of our world-class presence in both cancer nanotechnology and skin disease research,” said Paller, a member of the Center for Genetic Medicine. “By capitalizing on our strengths at Northwestern, with the help from a small NIH-funded pilot grant, we were able to apply Chad’s nanostructures to skin disease, and now the rest is history.”

Northwestern has one of nine Centers of Cancer Nanotechnology Excellence funded by the NIH and one of six Skin Disease Research Centers funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Mirkin and Paller are both members of the Robert H. Lurie Comprehensive Cancer Center.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Cancer Institute and the Army Research Office supported this research. The NU-SDRC provided core resources and a pilot grant.

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