RALEIGH — A new approach to designing anti-cancer drugs developed by researchers at N.C. State University and UNC-Chapel Hill shows just how complex the products of the rapidly emerging field of engineered drug therapies can be.
The nanoparticle they created is essentially a tiny machine that performs a sequence of tasks in a pre-set, specific order to overcome cancer cells. It persuades a cancer cell to latch onto it, then it uses first one method, then another to kill the cells.
“They are programmed almost like a computer so that they tackle the problem step by step,” said Zhen Gu, senior author of a paper on the research and an assistant professor in the joint biomedical engineering program at both universities.
The particle isn’t exactly a drug itself. Tianyue Jiang, a lead author of the paper who works in Gu’s lab, calls it a “drug delivery vehicle.”
Its unusual nature was underlined by the type of journal in which the scientists published their research: It appears not in a pharmaceutical journal or one on biological research, for example, but in the current edition of the bi-monthly “Advanced Functional Materials.”
The paper details the nature of the nanoparticle and the results when Gu’s research team tested it on human breast-cancer tumors in mice. It was significantly more effective than conventional treatment techniques in reducing the tumors.
Gu said that his team wanted to develop an effective way to target cancer cells simultaneously with multiple drugs, an approach that is less likely to provoke the cancer to develop resistance than if a single drug is used.
But different drugs often target different parts of a cancer cell. Delivering two drugs at essentially the same time to different parts of a cell, his team thought, may be possible with a cleverly-engineered nanoparticle.
The one they developed has an outer shell made of an acid woven together with a protein drug called TRAIL. The acid interacts with receptors on the outer membranes of cancer cells, tricking them into binding to the nanoparticle. Then enzymes around the cancer cell break down the acid, releasing the drug onto the cell membrane. That eventually kills the cell.
But the nanoparticle also packs a second deadly punch.
When its outer shell of acid and TRAIL breaks down, that reveals a core which is made of yet another cancer-fighting drug, called Dox, embedded with a material that helps the core penetrate the outer membrane of the cancer cell. Once inside, the Dox can enter the nucleus of the cell, killing it.
Studies with mice don’t necessarily correspond with similar results in humans but are an early step in researching such drugs. The research team plans to try the technique next on human breast cancer cells in larger animals, Gu said. They also believe it holds significant promise for treating other cancers, such as leukemia and prostate cancer.
“The early results are very promising, and we think this could be scaled up for large-scale manufacturing,” he said.