Lewis Katz School of Medicine Researchers Investigate Use of Nanoengineered Stem Cells as ‘Trojan Horse’ for Targeted Drug Delivery

An ongoing challenge of cancer treatment is finding a way to use powerful chemotherapies to attack tumor cells while minimizing toxic side effects. A recent study by researchers at the Lewis Katz School of Medicine at Temple University and Fox Chase Cancer Center has demonstrated a potential new way to avoid this problem by using nanoengineered stem cells as a drug delivery system.

Nanoengineering refers to the use of stem cells on the nanoscale, which is used to measure some of the smallest objects—one nanometer is one billionth of a meter.

Previous clinical trials of mesenchymal stem cells (MSCs) found they were safe, but that they were not effective as a tool for cancer drug delivery because they didn’t target tumors efficiently. But the new study identified a different way of nanoengineering and loading the cells that improves their ability to home in on the tumor site and successfully deliver their drug payload.

“Based on what has been found in prior clinical trials with naive MSCs, which are not engineered in the way ours are engineered, we believe our MSCs will work better,” said Swayam Prabha, MBA, PhD, lead author on the study and an associate professor at the Fels Cancer Institute for Personalized Medicine at the Katz School of Medicine.

For the study, Prabha and the research team loaded MSCs with paclitaxel, a powerful chemotherapy drug. In addition to being a common frontline treatment for lung and other cancers, the choice had a personal connection for Prabha—it’s the drug one of her relatives received during treatment for ovarian cancer.

“Despite being a 17-year survivor, she still has nerve numbness and reduced mobility in her limbs,” said Prabha, who is also an associate professor in the Cancer Signaling and Microenvironment research program at Fox Chase. “It’s a great standard-of-care treatment, but we have to give such high doses that it leads to some toxic side effects that can have an impact on the patient’s quality of life.”

Stem cells offer a potential solution because they have the ability to target and enter cancer cells while shielding themselves from attack. By acting as a “Trojan horse” and delivering drugs directly into the tumor, they could open the door for lower doses of some toxic medications like paclitaxel.

Previous clinical studies of the technology found that naturally occurring MSCs weren’t good enough at homing in on tumor cells to be a viable treatment option. However, for the new study, scientists used nanoengineering to load the MSCs with the paclitaxel molecule. They found that these engineered MSCs were more effective at killing tumors in mice and investigated further to understand why.

When they took a closer look at what was happening at the molecular level, they found that when the engineered MSC was loaded with the toxic drug, it triggered a stress response in the cell. This in turn caused the cell to uptake higher levels of two proteins, one which protects the cell from damage and another which improves its tumor-homing ability.

“Our MSC actually acts as a sponge, absorbing these proteins and using them to its advantage to allow it to home in on the tumor and not get killed in the process,” Prabha said.

The results came as a surprise, she added, since other research has focused on finding ways of genetically modifying MSCs to increase these proteins with limited success. “We never thought that our vector would have just an inherent ability to increase uptake without us doing anything to it.”

Next, Prabha and her team hope to further enhance this “sponge effect,” making it more effective. They also want to test the technology in clinical trials with the hope of demonstrating improved homing in human tumors.

“In the big picture we are working toward the day that cancer patients don’t have all these side effects, especially limb numbness, and we don’t have to give cancer patients so much pain medication,” she said. “Ultimately, our goal is to make patients’ lives better and give them a better quality of life.”

The study, “Incorporation of Paclitaxel in Mesenchymal Stem Cells Using Nanoengineering Upregulates Antioxidant Response, CXCR4 Expression and Enhances Tumor Homing,” was published in Materials Today Bio.