By Tom Ulrich
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.
Daniel Kohane, MD, PhD, a critical care specialist and director of the Laboratory for Biomaterials and Drug Delivery at Boston Children’s Hospital, thinks he’s hit upon a promising trigger, one that’s all around us: light.
A spectrum of possibilities
The light we see represents only a narrow slice of the electromagnetic spectrum. Move up just beyond the red wavelengths and you enter the near infrared (NIR) range of the spectrum. Move just below violet, and you’re into ultraviolet (UV) light.
Both kinds of light have advantages and disadvantages as possible drug delivery and activation triggers. Our tissues are relatively transparent to NIR light, allowing it to penetrate deep into the body, but it doesn’t pack much power.
UV light, on the other hand, is highly energetic, able to break chemical bonds—say, between a drug molecule and a carrier or nanoparticle.
UV’s power, though, is also its downside: It readily damages cells at the nuclear level, and so can only be used in short bursts. It also doesn’t penetrate tissues as well as NIR.
“It’s a tradeoff,” says Kohane. “When designing a light-activated system, you have to decide on what you’ll need: the ability to penetrate or the ability to manipulate.”
This (nano) light of mine…
At a recent showcase put together by Boston Children’s Innovation Acceleration Program (IAP), Kohane’s laboratory displayed three technologies that mix light and nanomaterials to improve drug penetration and accumulation:
- Drug-toting nanoparticles that shrink in UV light, penetrating tumors’ abnormal blood vessels while squeezing out their drug payload. In a study published last year in theProceedings of the National Academy of Sciences (PNAS), Kohane and postdoctoral fellow Rong Tong, PhD, showed that the nanoparticles greatly increased tumor penetration and accumulation of docetaxel in a mouse model of sarcoma compared to injecting the drug alone.
- An implantable drug reservoir whose membrane, impregnated with gold nanoparticles, opens up when stimulated with NIR light. Described earlier this year by Kohane and instructor Brian Timko, PhD, in anotherPNAS paper, the device provides on-demand, repeatable and tunable drug dosing that had a significant impact on blood sugar levels in a rat model of type 1 diabetes.
- Nanoparticles that bind to cell surface proteins when exposed to UV light. First reported by Kohane and former postdoc Tal Dvir, PhD (now at Tel Aviv University), in a 2010 paper in Nano Letters, the nanoparticles are coated with a specific peptide sequence that is then chemically masked. UV light removes the mask, freeing the peptide to bind the nanoparticles to the cell surface. The technology would allow doctors to target a drug for delivery to specific tissues by shining a light on a patient’s body where they want the drug to go.
Kohane isn’t just looking to light and nanoscale materials for ways to deliver treatment—he wants to use them as a means of treatment in and of themselves. For instance, he and fellow Doris Gabriel, PhD, have developed nanomaterials that, when lit up with NIR light, basically clean themselves by releasing molecules called reactive oxygen species. The materials, described by Gabriel and Kohane in Advanced Healthcare Materials and Biomaterials, could be used to build cardiovascular stents that don’t clot or catheters that don’t get fouled with bacteria.
And last year Kohane and postdoc Dong-Kwon Lim, PhD, showed in Nano Letters that nanoparticles made of gold shells and rods coated with a thin layer of graphene (a form of carbon), could—if properly targeted—be heated up with NIR light and used to cook diseased cells.
In addition to their origins in a mix of light and nanoscience, there’s one thing all of these technologies have in common: an end goal of making drugs better and safer for patients.
“The ability to combine drug targeting and triggering technologies will allow greater drug efficacy while minimizing drug toxicity,” Kohane says.