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Bind cofounder Omid Farokhzad, associate professor at Brigham Women’s Hospital and Harvard Medical School, came up with the novel method for building nanoparticles while he was a postdoctoral researcher in the lab of Robert Langer, an MIT chemical engineering professor. Langer’s group had already developed nanoparticles capable of releasing drugs in a controlled manner, but the particles did not yet seek out cancer cells specifically. Farokhzad’s first challenge was to create nanoparticles whose molecular instructions would bring them to cancer cells, but which remained anonymous within the bloodstream so that the immune system wouldn’t destroy them. The second was coming up with a robust and reproducible manufacturing process.

Instead, Farokhzad and Langer devised a method by which the building blocks of the nanoparticle and the drug self-assemble into a final product. Two types of polymer combine to form the tangled mesh of Bind’s drug-laden spherical nanoparticle. One of these polymers has two chemically and structurally distinct regions, or “blocks”: a water-insoluble block that forms part of the mesh that encapsulates the drug, and a water-soluble block that gives the final product a stealthy corona to evade the immune system. The other type of polymer has three blocks: the same two as the first, as well as a third region that contains a targeting molecule—the signal that will ensure the final particles attach to the desired cell types. The drug-carrying nanoparticles are formed by simply mixing these polymers together with the drug in the appropriate conditions.

The self-assembling polymers can be produced in a repeatable and scalable fashion. But the method has an additional benefit, one that may be the real key to Bind’s success. The method by which the nanoparticles are built—from individual preparations of the two-block and three-block polymers—would also let researchers use high-throughput screening approaches, akin to how medicinal chemists design and test new drug compounds. Each block could be tweaked—extend one block, change the charge on another—and the relative amounts of each polymer could be varied. With so many parameters for tinkering, Bind’s scientists can screen many combinations.

Its first drug in clinical trials, Bind-014, carries a widely used chemotherapeutic called docetaxel through the bloodstream to cancer cells. The drug is packaged inside a ball-like nanostructure made of biodegradable polymers that protect the drug and shield it from the body’s immune system. The external surface of each nanoparticle is dotted with molecules that target cancerous cells. Once the nanoparticle has reached its target, it sticks to the outside of the cell, which triggers the cell to engulf the particle. The drug diffuses out of the particle at a controlled rate and is released into the deranged cell.

Mark Davis, a professor of chemical engineering at Caltech, is hopeful that the few ongoing trials of targeted nanoparticle therapeutics, which include one developed in his lab as well as Bind-014, will demonstrate the technology’s potential. “The medical community isn’t going to get excited until there is [an advanced human trial] where we can show what these targeted nanoparticles actually do for patients in a statistically significant way.” For now, the results from the 17 patients enrolled in the phase I trial of Bind-014 look promising, but a real test of efficacy will have to wait until phase II trials, which are likely to start later this year.

The “programmable” design used by Bind may be key to bringing more nanoparticle-targeted drugs to trial. The company’s methods could be applied to any existing drugs or compounds, including those that may have been shelved by pharmaceutical companies because they proved too toxic to the whole body. “We believe we can have a very broad platform of drugs that we can develop,” says Hrkach.

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Credit: Model & image by Digizyme, Inc.

Tagged: Biomedicine, nanoparticles, nanomedicine

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