News Feature: Cancer nanomedicine, reengineered

The miniature craft cruises silently through a blood vessel. Sneaking through a hole in the vessel wall, it infiltrates a tumor and uses an on-board antibody key to gain entry into a cancer cell. Once inside, the sleek ship deploys its anticancer cargo to destroy the tumor. Mission accomplished. This vision of nanomedicine, commonly portrayed in animations from the early 2000s, promised that nanotechnology would be cancer’s magic bullet, giving us therapies that could identify the site of disease, travel there, and wipe it out. Omid Farokhzad, a physician and biomaterials researcher at the Brigham and Women’s Hospital in Boston, says he now feels embarrassed when he sees such videos. “Fifteen years ago, our concept was that if we put some tumor-targeting ligands on the surface of a nanoparticle, it would get into a cell,” says Farokhzad. “That is incredibly naïve.” In principle, nanomedicine could deliver a drug (or even a combination of drugs) precisely where it’s needed in the body. This increases a drug’s effectiveness while avoiding side effects caused by flooding the entire body with a conventional chemotherapy, all this by virtue of their size. One of the field’s core assumptions is that nanoparticles are small enough to leak through shoddily built blood vessels around tumors, but too big to pass through normal vasculature into healthy tissues. Based on this passive targeting principle, the field has had a handful of clinical successes that rely on bulky nanoparticle carriers to keep toxic cancer drugs out of the heart and other off-target tissues. But at the same time, researchers want to improve the nanoparticle’s active targeting of tumor tissue, which has been much more difficult to achieve. Until recently, the messy biology of real human tumors has repulsed most attempts. So researchers are trying a fresh approach, reengineering nanomedicine using data about how nanoparticles interact with tissues and cells. They’re also striving to understand why nanomedicine works in some patients and tumors but fails in others.While shrugging off the field’s more fantastical visions, nanomedicine researchers now hope to make more effective, targeted therapies that live up to their name.