Researchers at the Georgia Institute of Technology have developed a targeted therapy using nanohydrogels to stunt the growth of ovarian tumors in in vivo tests in mice, according to a new study.
The nanohydrogel is a gel pellet that researchers can load with RNA to carry into cancer cells and knock down a particular protein.
“The dramatic effect we see is the massive reduction or complete eradication of the tumor, when the ‘nanohydrogel’ treatment is given in combination with existing chemotherapy,” chief researcher John McDonald said in prepared remarks.
The study, published in Scientific Reports, describes a method using therapeutic short interfering RNA (siRNA) to thwart the overproduction of epidermal growth factor receptors (EGFS).
“In many cancers, EGFR is overexpressed,” McDonald said. “The problem is that because of this overexpression, many cellular functions, including cell replication and resistance to certain chemotherapy drugs, are dramatically cranked up.” In fact, McDonald said, EGFR is overexpressed in 70% of ovarian cancer patients.
“The platinum-based chemotherapies used to treat ovarian cancers cause DNA damage, which switches on apoptosis,” McDonald explained.”EGFR overexpression hinders apoptosis; they won’t die. By knocking down EGRF, we make the cell hypersensitive to the drug. Apoptosis is reactivated,”
In other words, traditional chemotherapy treatments treat cancer by triggering the cells natural defense mechanism – apoptosis, or cell suicide. But, if a cell is overexpressing EGFR, the apoptosis mechanism won’t work. Getting rid of the overexpressed EGRF stops the cell from becoming chemoresistance and enables the cells’s ability to die again.
“We’re knocking down EGFR at the RNA level,” McDonald said. “Since EGFR is multi-functional, it’s not exactly clear which malfunctions contribute to ovarian cancer growth. By completely knocking out its production in ovarian cancer cells, all EGFR functions are blocked.”
The nanohydrogel delivery vessel is nearly 98% water, according to the team, and is a colloidal ball of compact organic molecules. A guide molecule is added to the surface, making the pellets adhere to the cancer cells. During the in vivo trials, researchers tagged the siRNA with a fluorescent tag to visualize the nanohydrogels targeting the cancerous cells.
“When you get into a tumor, there are a lot of blood vessels, and many are broken,” McDonald added. “This may help the nanoparticles get passively trapped in the neighborhood of tumorous tissues.”
While the technique was successful in mice, it will take a lot more effort before the team can move forward in a clinical trial with patients.
“When we gave the chemotherapy alone, the response was moderate, but with the addition of the nanoparticles, the tumor was either significantly reduced or completely gone,” McDonald said. “Further work will be required to see if the treatment completely destroyed every trace of cancer cells in the tumors that disappeared, or if future recurrence is possible.”
