Nanomedicine
Building Nanoparticles for Kidney Disease
Posted on by Dr. Francis Collins
Great things sometimes come in small packages. That’s certainly true in the lab of Eun Ji Chung at the University of Southern California, Los Angeles. Chung and her team each day wrap their brains around bioengineering 3-D nanoparticles, molecular constructs that measure just a few billionths of a meter.
Chung recently received an NIH Director’s 2018 New Innovator Award to bring the precision of nanomedicine to autosomal dominant polycystic kidney disease (ADPKD), a relatively common inherited disorder that affects about 600,000 Americans and 12 million people worldwide.
By age 60, about half of those battling ADPKD will have kidney failure, requiring dialysis or a kidney transplant to stay alive. For people with ADPKD, a dominantly inherited gene mutation causes clusters of fluid-filled cysts to form in the kidneys that grow larger over time. The cysts can grow very large and displace normal kidney tissue, progressively impairing function.
For Chung, the goal is to design nanoparticles of the right size and configuration to deliver therapeutics to the kidneys in safe, effective amounts. Our kidneys constantly filter blood, clearing out wastes that are removed via urine. So, Chung and her team will exploit the fact that most molecules in the bloodstream measuring less than 10 nanometers in diameter enter the kidneys, where they are gradually processed and eliminated from the body. This process will give nanoparticles time to bind there and release any therapeutic molecules they may be carrying directly to the cysts that cluster on the kidneys of people with ADPKD.
Chung’s research couldn’t be more timely. Though ADPKD isn’t curable right now, the Food and Drug Administration (FDA) last year approved Jynarque™ (tolvaptan), the first treatment in the United States to slow the decline in kidney function in ADPKD patients, based on tests of the rate of kidney filtration. Other approved drugs, such as metformin and rapamycin, have shown potential for repurposing to treat people with ADPKD. So, getting these and other potentially life-saving drugs directly to the kidneys, while minimizing the risk of serious side effects in the liver and elsewhere in the body, will be key.
Most FDA-approved nanoparticle therapies are administered intravenously, often for treatment of cancer. Because ADPKD is chronic and treatment can last for decades, Chung wants to develop an easy-to-take pill to get these nanoparticles into the kidneys.
But oral administration raises its own set of difficulties. The nanoparticles must get from the stomach and the rest of the gastrointestinal tract to the bloodstream. And then if nanoparticles exceed 10 nanometers in diameter, the body typically routes them to the liver for clearance, rather than the kidneys.
While Chung brainstorms strategies for oral administration, she’s also considering developing a smart bandage to allow the nanoparticles to pass readily through the skin and, eventually, into the bloodstream. It would be something similar to the wearable skin patch already featured on the blog.
In the meantime, Chung continues to optimize the size, shape, and surface charge of her nanoparticles. Right now, they have components to target the kidneys, provide a visual signal for tracking, enhance the nanoparticle’s lifespan, and carry a therapeutic molecule. Because positively charged molecules are preferentially attracted to the kidney, Chung has also spent untold hours adjusting the charge on her nanoparticles.
But through all the hard work, Chung and her team continue to prove that great things may one day come in very small packages. And that could ultimately prove to be a long-awaited gift for the millions of people living with ADPKD.
Links:
Polycystic Kidney Disease (National Institute of Diabetes and Digestive and Kidney Diseases/NIH)
Video: Faculty Profile – Eun Ji Chung (University of Southern California, Los Angeles)
Chung Laboratory (USC)
Chung Project Information (NIH RePORTER)
NIH Director’s New Innovator Award (Common Fund)
NIH Support: Common Fund; National Institute of Diabetes and Digestive and Kidney Diseases
Nanodiamonds Shine in Root Canal Study
Posted on by Dr. Francis Collins
Caption: An artistic rendering of nanodiamonds
Credit: Ho Lab
When the time comes to get relief from a dental problem, we are all glad that dentistry has come so far—much of the progress based on research supported by NIH’s National Institute of Dental and Craniofacial Research. Still, almost no one looks forward to getting a root canal. Not only can the dental procedure be uncomfortable and costly, there’s also a risk of failure due to infection or other complications. But some NIH-supported researchers have now come up with what may prove to be a dazzling strategy for reducing that risk: nanodiamonds!
That’s right, these researchers decided to add tiny diamonds—so small that millions could fit on the head of the pin—to the standard filler that dentists use to seal off a tooth’s root. Not only are these nanodiamonds extremely strong, they have unique properties that make them very attractive vehicles for delivering drugs, including antimicrobials that help fight infections of the sealed root canal.
NIH Common Fund: 10 Years of Transformative Science
Posted on by Dr. Francis Collins
Happy 10th Anniversary to the Common Fund! It’s hard to believe that it’s been a decade since I joined then-NIH Director Elias Zerhouni at the National Press Club to launch this trans-NIH effort to catalyze innovation and speed progress across many fields of biomedical research.
We’re marking this milestone with a special celebration today at NIH’s main campus. And, for those of you who can’t make it to Bethesda to join in the festivities, you can watch the videocast (live or archived). But allow me also to take this opportunity to share just a bit of the history and a few of the many achievements of this bold new approach to the support of science.
