Critical to the treatment's success is the ability to package two completely different kinds of molecules--large, water-soluble proteins like IL-2 and tiny, water-phobic molecules like the TGF-β inhibitor-into a single package.
While many NLGs are injected into a patient during treatment, each one is a sophisticated system composed of simple-to-manufacture, yet highly functional, parts. The outer shell of each NLG is made from an FDA-approved, biodegradable, synthetic lipid that the researchers selected because it is safe, degrades in a controlled manner, is sturdy enough to encapsulate a drug-scaffolding complex, and is easy to form into a spherical shell.
Each shell surrounds a matrix made from biocompatible, biodegradable polymers that the engineers had already impregnated with the tiny TGF-β inhibitor molecules. The researchers then soaked those near-complete spheres in a solution containing IL-2, which gets entrapped within the scaffolding, a process called remote loading.
The end result is a nanoscale drug delivery vehicle that appears to fit the narrow parameters necessary for successful treatment. Each NLG is small enough to travel through the bloodstream, yet large enough to get entrapped in leaky cancer blood vessels.
The NLG lipid shells have the strength to carry drugs into the body, yet are degradable so that they can deliver their cargo. And most critically, the spherules are engineered to accommodate a wide range of drug shapes and sizes. Ultimately, such a system could prove powerful not only for melanoma, but for a range of cancers.
|Contact: Josh Chamot|
National Science Foundation