Most nanoparticle delivery systems in development that target tumors rely on using antibodies to bind specific receptors on cancer cells. This allows the therapeutic particles to both get to the tumor site and to stick to it.
A new technique in development at University of California, San Diego instead uses novel materials that change shape in response to the presence of enzymes commonly found in some cancers. The particles that are injected into the blood stream originate in a spherical shape, but when they get to the tumor they open up to link up into a scaffold whose shape blocks its passage further down the blood stream. Such technique may allow drugs to be ferried directly to tumor sites and nanoparticles to gather that can then be energized to ablate the diseased tissue around them.
More details about the technology from UCSD:
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 in that configuration can easily be injected into a vein.
When mixed with MMPs in vials, the enzymes nicked the peptides on the surface of the spheres, which reassembled into netlike threads.
The team tested the concept further by injecting their new nanoparticles into mice with human fibrosarcomas, a kind of cancer that produces high levels of MMPs.
To mark when the spheres broke down to form other structures, the chemists placed one of two fluorecent dyes, rhodamine or fluorescein, inside the spheres. In close proximity, the dyes interact to create a specific light signal called FRET for Förster Resonance Energy Transfer, when energy jumps from rhodamine to fluorescein.
Within a day they detected FRET signals indicating that the spheres had reassembled at the sites of the tumors, and the signal persisted for at least a week.
The treatment is not inherently toxic. It did not appear to change the tumors in any way, and liver and kidney, the organs most vulnerable to collateral damage from treatments because they clear toxins from the body, were normal and healthy eight days after injection.
Study in Advanced Materials: Enzyme-Directed Assembly of a Nanoparticle Probe in Tumor Tissue
Read on from UCSD: Shape-shifting Nanoparticles Flip from Sphere to Net in Response to Tumor Signal