The Penn State team used one of cancer's biggest strategies against it. The researchers developed a way to camouflage their cancer-killing drug by hiding it in the cells of the tumor. This lets the drug get past the tumor's natural preservation and safety mechanisms and deliver the drug from inside the tumor itself.
The team, led by Siyang Zheng, used a unique protein toxin called gelonin -- something found most commonly in a plant in the Himalayan mountains. The gelonin let researchers cage the proteins within a nanoparticle framework that would protect the drug from the body's immune system. To top it all off and make sure the drug was delivered to the tumor, the metal-organic framework (MOF) nanoparticles were coated in the tumor's cells.
"We designed a strategy to take advantage of the extracellular vesicles derived from tumor cells."
"We designed a strategy to take advantage of the extracellular vesicles derived from tumor cells," said Zheng, associate professor of biomedical and electrical engineering at Penn State. "We remove 99 percent of the contents of these extracellular vesicles and then use the membrane to wrap our metal-organic framework nanoparticles. If we can get our extracellular vesicles from the patient, through biopsy or surgery, then the nanoparticles will seek out the tumor through a process called homotypic targeting."
After a medical professional gives the nanoparticle drug, the MOF will float around in the bloodstream until it finds the tumor. Then, it adheres to the cell membrane. The cancer cells will then consume the nanoparticle during a process called endocytosis. The higher acidity of the inside of the cell then breaks down the metal-organic framework, the nanoparticles, and thus the toxic Himalayan protein that then kills the cell.
Gong Cheng, lead author on a new paper describing the team's work and a former post-doctoral scholar in Zheng's group now at Harvard, said, "MOF is a class of crystalline materials assembled by metal nodes and organic linkers. In our design, self-assembly of MOF nanoparticles and encapsulation of proteins are achieved simultaneously through a one-pot approach in aqueous environment."
"The enriched metal affinity sites on MOF surfaces act like the buttonhook, so the extracellular vesicle membrane can be easily buckled on the MOF nanoparticles," Cheng continued. "Our biomimetic strategy makes the synthetic nanoparticles look like extracellular vesicles, but they have the desired cargo inside."
Zheng and his team studied the results in small animal models first. However, they're hoping the success on the small scale could mean moving on to bigger subjects -- even if the size of the particles remains relatively small by comparison.
"Our metal-organic framework has very high loading capacity, so we don't need to use a lot of the particles and that keeps the general toxicity low," Zheng said.
The researchers said the concept of delivering drugs through the MOF framework could be used for other drugs that needed to get past the body's immune system.
The research was published in a recent edition of the Journal of the American Chemical Society.