Nanotech Particles in Topical Moisturizers Offer Hope of Gene Therapy

Nanotechnology has numerous applications in the fields of dermatology and medicine: sunscreen with nano-sized particles offers better protection, nanotech particles can provide topical vaccine delivery and nanotech-based creams can provide drug delivery to treat dermatologic conditions.

This week, a team led by a dermatologist and a chemist specializing in nanotechnology became the first to demonstrate that commercial nanotech-based moisturizers can deliver gene regulation technology that may prove effective in treating skin cancers such as melanoma and squamous cell carcinoma, plus potentially a host of other skin-based diseases.

“The technology developed by my collaborator Chad Mirkin and his lab is incredibly exciting because it can break through the skin barrier,” said Dr. Amy Paller, co-senior author of the paper scheduled to be published the week of July 2 in the Proceedings of the National Academy of Sciences.

“This allows us to treat a skin problem precisely where it is manifesting -- on the skin,” Dr. Paller, chair of dermatology and professor of pediatrics at Northwestern University Feinberg School of Medicine, said in a statement. “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.”

It’s very difficult to deliver gene regulation therapy topically, since the skin is designed to defend against substances that attempt to penetrate it.

The approach developed at Northwestern uses drugs that consist 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.

Normal, linear nucleic acids cannot get into cells, but these spherical nucleic acids can. The technique uses a small molecule of RNA with highly oriented, densely packed nucleic acids that form a tiny sphere around a gold nanoparticle. The RNA’s sequence is programmed to target the disease-causing gene.

When these specially designed drugs are applied to the skin, they are able to penetrate all of the skin’s layers. In addition, they can target disease-causing genes selectively while ignoring “normal” genes. Once the drugs have penetrated into cells, they function by turning off the genes that cause and promote skin cancers.

“We now can go after a whole new set of diseases,” said Dr. Chad Mirkin, director of Northwestern’s International Institute for Nanotechnology, in a statement. “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.”

Initially, Dr. Paller and Dr. Mirkin hope to develop treatments for melanoma and squamous cell carcinoma using the technology. Eventually, the nanotech-based drugs could treat the autoimmune skin disorder psoriasis, diabetic wounds and even epidermolytic ichthyosis, a rare genetic skin disorder with no current effective treatment.

And yes, the nanotech drugs may treat wrinkles eventually, as well.

So far, the researchers have conducted experiments with the nanostructures (combined with a commercial moisturizer) on both mice and humans. In those experiments, the nanostructures were designed to target epidermal growth factor receptor (EGFR), a biomarker associated with a number of cancers.

In both the mice and the humans, the drug was able to break through the epidermal layer and penetrate the skin deeply. Cells took up 100% of the nanostructures, which down-regulated the EGFR gene and decreased production of the cancer-associated proteins.

The experiments produced no evidence of side effects after one month’s continued application of the nanotech-spiked moisturizer – the drug didn’t trigger the immune system or cause the nanoparticles to accumulate in organs. According to the researchers, the treatment is skin-specific and doesn’t interfere with other organs or cells.

Dr. Mirkin first developed the nanostructure platform used in this study in 1996, and its capabilities currently are used in commercialized medical diagnostic tools. For example, nanostructures arrayed on a single assay can provide a much more sensitive cancer detection device than older technologies. In addition, nanopore structures are being used in rapid, accurate DNA sequencing.

However, this study involves nanotech particles that actually penetrate the skin, delivering what its developers call “a large payload” of therapeutics.

“The field of medicine needs new constructs and strategies for treating disease,” Dr. Mirkin. “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.”

Sources:

Bellah M. et al. Nanostructures for Medical Diagnostics. Journal of Nanomaterials. 2012. doi:10.1155/2012/486301.

Nasir A. The Future of Nanotechnology in Dermatology. U.S. Dermatology Touch Briefings. 2008.

Northwestern University press release. “Breaking the Skin Barrier.” July 2, 2012.