Scientists at the University of California, San Diego, have designed tiny spherical particles to float easily through the bloodstream after injection, then assemble into a durable scaffold within diseased tissue. An enzyme produced by a specific type of tumor can trigger the transformation of the spheres into netlike structures that accumulate at the site of a cancer, the team reports in the journal Advanced Materials this week.
Targeting treatments specifically to cancerous or other diseased cells depends on some means of accumulating high levels of a drug or other therapeutic agent at the specific site and keeping it there. Most efforts so far depend on matching a piece of the drug-delivering molecule to specific receptors on the surface of the target cell.
Inspiration for this new strategy came from biological systems that use shape to alter the ability of something to lock in place or slip away and escape, said Nathan Gianneschi, a professor of chemistry and biochemistry, who led the project.
"We wanted to come up with a new approach," Gianneschi said. "Specifically, we wanted to design switchable materials that we could inject in one shape and have them change to another between the blood and tumors."
Some cancerous tissues produce high levels of a class of molecules called MMPs, for matrix metalloproteinases. These enzymes change how other proteins behave by altering their molecular configuration, leading to metastasis. Gianneschi and colleagues harnessed this ability to alter their nanoparticles in ways that would cause them to linger at the site of the tumor.
"We figured out how to make an autonomous material that could sense its environment and change accordingly," Gianneschi said.
Each nanoparticle is made of many detergent-like molecules with one end that mixes readily with water and another that repels it. In solution, they self assemble into balls with the water-repellant ends inside, and
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University of California - San Diego