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Nanoscale Drug Delivery Process Helps Cancer Treatment

Tarek Fahmy (Yale University)

Tarek Fahmy (Yale University)

Researchers from Yale University’s medical and engineering faculties in New Haven have devised a new technique for delivering cancer treatments that also boosts a response by the immune system. The findings of the research, funded by a National Science Foundation grant, and led by Yale University biomedical engineering professor Tarek Fahmy (pictured right) are found online in the journal Nature Materials; paid subscription required.

The new methods aim to counter secretions of chemicals by cancerous tumors that confuse the immune system and limit or impede the treatments to battle those tumors. The technique developed by Fahmy’s team has shown on tests with mice it can simultaneously deliver a sustained dose of cancer fighting chemicals and an immune system booster, something the researchers say has rarely been successful before.

The Yale team developed nanoscale, hollow, biodegradable spheres called nanolipogels, each one able to carry quantities of drugs made from chemically diverse molecules. The outer shell of the nanolipogel is made from an FDA-approved, biodegradable, synthetic lipid — a water-phobic substance such as fats and oils — that is safe, degrades in a controlled manner, sturdy enough to carry a drug-supporting matrix, and easy to form into a spherical shape. Inside the shell is the drug-carrying matrix scaffold made of biocompatible and biodegradable polymers.

The nanolipogels used in the Yale experiments carried two compounds: (1) an inhibitor of transforming growth factor-beta, a defensive chemical emitted by tumors, and (2) interleukin-2, an immune-system booster and cell-signaling protein used in cancer treatments. Fahmy describes transforming growth factor-beta as the moat around the castle, in this case the tumor, with the inhibitor serving to dry up the moat, so the interleukin-2 can work. “The inhibitor,” says Fahmy, “effectively stops the tumor’s ability to stunt an immune response.”

That immune response is made possible at the same time by interleukin-2. Continuing with the moat and castle analogy, Fahmy says interleukin-2 “can be thought of as a way to get reinforcements to cross the dry moat into the castle and signal for more forces to come in.” The reinforcements in this case are the body’s T lymphocytes or T-cells, the white blood cells that help the immune system fight diseases.

The researchers impregnated the drug-carrying matrix with the transforming growth factor-beta inhibitor molecules. The team then soaked the spheres in a solution containing interleukin-2, which gets trapped inside the scaffolding, in a process called remote loading.

The Yale team tested the nanolipogel delivery on mice with primary melanoma cancers and melanomas that have spread to the lung, but not primary lung cancers. The drug-carrying spheres were found to accumulate in the leaky blood vessels of tumors, where they released the onboard compounds in a controlled, sustained fashion as the walls and scaffolding of the spheres broke down in the blood stream.

Fahmy and colleagues found the nanolipogel delivery in the test mice delayed tumor growth, sent tumors into remission, and increased survival rates. The technology, subject to further testing and clinical trials, appears to be suited for immunotherapy on cancers, such as metastatic cancers, where radiation, chemotherapy, and surgery tend to prove unsuccessful.

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