Researchers at Northwestern University have discovered a way to deliver gene regulation technology through topical moisturizers. Although the technology was initially investigated to treat melanoma, squamous cell carcinoma, psoriasis, diabetic wound healing and epidermolytic ichthyosis, it may also be used to treat wrinkles in aged skin.
The technology is detailed in “Topical Delivery of siRNA-based Spherical Nucleic Acid Nanoparticle Conjugates for Gene Regulation,” an article appearing in the Proceedings of the National Academy of Sciences (PNAS). It delivers drugs comprised of novel spherical arrangements of nucleic acids. These structures bind to natural proteins that allow them to penetrate the skin and enter cells. When topically applied, the drug penetrates the skin’s layers to selectively target disease-causing genes while sparing normal genes.
The technology was originally developed by Chad Mirkin, the George B. Rathmann professor of chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering. He also is the director of Northwestern’s International Institute for Nanotechnology and co-senior author of the paper. Mirkin first developed the nanostructure platform used in this study in 1996 at Northwestern, and the technology now is the basis of powerful commercialized medical diagnostic tools. This, however, is the first realization that the nanostructures naturally enter skin and that they can deliver a large payload of therapeutics.
The delivery system is able to penetrate the skin due to the nanostructure’s spherical shape and nucleic acid density. Normal (linear) nucleic acids cannot enter cells, but these spherical nucleic acids can. Small interfering RNA (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.
The nanostructures were were combined with a commercial moisturizer with the help of co-senior author Amy S. Paller, MD, the Walter J. Hamlin professor, chair of dermatology and professor of pediatrics at Northwestern University Feinberg School of Medicine. She also is director of Northwestern’s Skin Disease Research Center.
The researchers applied the therapeutic ointment to the skin of mice and to human epidermis. The nanostructures were designed to target epidermal growth factor receptor (EGFR), a biomarker associated with a number of cancers. In both cases, the drug broke through the epidermal layer and penetrated the skin very deeply, with cells taking up 100% of the nanostructures. They selectively knocked down the EGFR gene, decreasing the production of the problem proteins.
After a month of continued application of the ointment, there was no evidence of side effects, inappropriate triggering of the immune system or accumulation of the particles in organs. The treatment is skin specific and does not interfere with other cells.
The researchers believe the technology offers a new way to treat skin disease. In addition, decades of genomic research have given the team a number of targets, for which they can adapt the sequence in the nucleic acid to treat.
In addition to Mirkin and Paller, other authors of the paper are Dan Zheng, David A. Giljohann, David L. Chen, Matthew D. Massich, Xiao-Qi Wang and Hristo Iordanov, all from Northwestern.