Programmable particle: Bind’s drug-delivery nanoparticle (artist’s rendering).
The results of the human trials are startling. Even at a lower-than-usual dose, multiple lung metastases shrank or even disappeared after one patient received only two-hour-long intravenous infusions of an experimental cancer drug. Another patient saw her cervical tumor reduce by nearly 60 percent after six months of treatment. Though the drug trial—by Bind Biosciences in Cambridge, Massachusetts—of an experimental nanotechnology-based technique was designed simply to show whether the technology is safe, the encouraging results revive hopes that nanomedicine could realize its elusive promise.
For more than a decade, researchers have been trying to develop nanoparticles that would deliver drugs more effectively and safely. The idea is that a nanoparticle containing a drug compound could selectively target tumor cells or otherwise diseased cells, and avoid healthy ones. Antibodies or other molecules can be attached to the nanoparticle and used to precisely identify target cells. “One of the largest advantages of nanotechnology is you can engineer things in particle form so that chemotherapeutics can be targeted to tumor cells, protecting the healthy cells of the body and protecting patients from side effects,” says Sara Hook, nanotechnology development projects manager with the National Cancer Institute.
“We make hundreds of combinations to evaluate in order to optimize the performance of each drug,” says Jeff Hrkach, senior vice president of technology research and development.
But executing this vision has been difficult. One challenge: a drug’s behavior in the body can change dramatically when it’s combined with nanoparticles. A nanoparticle can change a drug’s solubility, toxicity, speed of action, and more—sometimes beneficially, sometimes not. If a drug’s main problem is that it’s toxic to off-target organs, then nanotechnology can ensure that it’s delivered to diseased cells instead of healthy cells. But if a drug depends on being absorbed quickly by diseased cells to be effective, a nanoparticle may slow the process and turn an optimal therapeutic into second best.
Bind, which was launched in 2007, has attempted to overcome this problem by building its drug-targeting nanoparticles in a way that allows the company to systematically vary their structures and composition. Typically, targeted drug nanoparticles are produced in two steps: first, a drug is encapsulated in a nanoparticle, and second, the external surface of the particle is bound with targeting molecules that will steer the therapeutic ferry to diseased cells. Generating such nanoparticles can be difficult to control and replicate, which limits a researcher’s ability to fine-tune the nanoparticle’s surface properties. To avoid this pitfall, Bind synthesizes its drug-carrying nanoparticles using self-assembly.
Under the right conditions, the subunits of its nanoparticles—some of which already contain targeting molecules—assemble on their own. No complex and variable chemical reactions are needed to produce the nanoparticles, and the properties of each subunit can be tweaked. This also allows the company’s researchers to test a variety of nanoparticle-drug combinations and identify the best candidates for a particular task. “We make hundreds of combinations to evaluate in order to optimize the performance of each drug,” says Jeff Hrkach, senior vice president of technology research and development.