For the first time, scientists have shown that the elasticity of nanoparticles can affect how cells take them up in ways that can significantly improve drug delivery to tumors.
A team of Boston Children’s Hospital researchers led by Marsha A. Moses, PhD, who directs the Vascular Biology Program, created a novel nanolipogel-based drug delivery system that allowed the team to investigate the exclusive role of nanoparticle elasticity on the mechanisms of cell entry.
What if we could deliver biocompatible nanoparticles into the body and then activate them to release drugs exactly where they are needed, without causing side effects elsewhere?
Scientists like Daniel Kohane, MD, PhD, of Boston Children’s Hospital, are developing nanoscale drug delivery systems to do just that, using a variety of materials and triggers that are sensitive to a range of specific stimuli.
“Triggerable drug delivery systems could improve the treatment of many diseases by reducing side effects and increasing the effectiveness of therapeutics,” says Kohane, who directs the Laboratory for Biomaterials and Drug Delivery at Boston Children’s. He is the senior author on a recent article about the topic in Nature Reviews Materials.
One potential use of nanoscale drug delivery systems is of special interest to Kohane and his lab members …
You’ve just had a root canal or knee surgery — both situations that will likely require some sort of local pain medication. But instead of taking a systemic narcotic with all its side effects, what if you could medicate only the part of your body that hurts, only when needed and only as much as necessary?
That concept is today’s reality in the laboratory of Daniel Kohane, MD, PhD, professor of anesthesia at Harvard Medical School and a senior associate in pediatric critical care at Boston Children’s Hospital.
The Kohane laboratory is developing a patient-triggered drug delivery system — but not a simple time-release mechanism or one tethered to ports or pumps. Instead, around the time of an intervention, pain medication would be injected into the site, or around a nerve leading to that site. Whenever pain relief is needed, the patient triggers release of the drug with a laser-like light-emitting device. “It’s like carrying the pharmacy in your body,” explains Kohane. …
Getting drugs where they need to be, and at the right time, can be more challenging than you think. Tumors, for example, tend to have blood vessels that are tighter and twistier than normal ones, making it hard for drugs to penetrate them. Despite decades of research on antibodies, peptides and other guidance methods, drug makers struggle to target drugs to specific tissues or cell types.
And even once a drug arrives at the right place, the ability to fine-tune the dose so that the drug is released at the right time and in the right amount remains an elusive goal.
What’s needed is some kind of trigger, a stimulus that a clinician can turn on and off to guide when a drug is available and where it goes to make sure it does its job with the fewest side effects.
Part of the problem is that the methods available for treating sepsis aren’t particularly good. Antibiotics can kill the bacteria, but that still leaves bacterial debris floating in the bloodstream, fueling the already over-excited inflammatory response.
Removing the bacteria altogether—as fast as possible—would be the better solution. At least that’s what Daniel Kohane, MD, PhD, thinks. His lab at Boston Children’s Hospital’s Division of Critical Care Medicine has developed a new approach that combines magnetic nanoparticles, a synthetic molecule (called bis-Zn-DPA) that binds to the bacteria, and magnetized microfluidic devices to pull bacteria from the blood quickly and efficiently. …
Grab a garden hose. Put your thumb over the end, but not all the way, and turn the water on. What happens? The water coming out of the hose gets squeezed as it tries to push past your thumb, putting a lot of force on the molecules in the water and making a big spray.
Now do the same thing with an artery: Partially block it with a clot and let blood flow through it. In this case, the force you’ve created in the artery could be lethal—creating fertile ground for blood clots that could lead to a stroke or heart attack.