Cancer stem cells destroyed by drug-filled nanoparticles

A team of scientists has developed drug-carrying nanoparticles that can find and kill cancer stem cells, a tiny group of rare cells that can hide in tissue and cause cancer to return years after tumors have been treated.

In a paper published in the journal Molecular Cancer Therapeutics, researchers at the University of Illinois at Urbana-Champaign explain how they developed nanoparticles that can seek and latch on to a protein called CD44, which is found only on the surface of cancer stem cells.

The researchers loaded the nanoparticles with a drug that, by switching off certain genes in cancer stem cells, disabled their "stemness" so that they could no longer develop into new cancer cells. The drug — called niclosamide — is a common prescription medication used worldwide for treating tapeworm infection.

"To the best of our knowledge," says lead investigator Dipanjan Pan, a professor of bioengineering, "this is the first demonstration of delivering cancer stem-cell-targeted therapy with a nanoparticle."

Cancer stem cells and 'stemness'

Stem cells are a remarkable group of undifferentiated cells that are capable of specializing into other types of cell. They are different from other cells in that they can renew themselves by dividing, even if they have been inactive for a long time.

Cancer stem cells are also stem cells that are able to replenish themselves through division and differentiate into other cell types — except that, in their case, they make cells that form tumors.

As they have been found in several types of cancer tumors in patients, researchers have become increasingly interested in them as targets for new cancer treatments.

Stemness is the unique feature of stem cells that allows them to replenish themselves through division, become differentiated cell types, and interact with their environment in ways that let them remain dormant or progress into cancer.

Because of stemness, it "only takes one or two" cancer stem cells to hide in tissue and "seed a new tumor," even long after treatment of the original tumor.

To vastly reduce, or perhaps even remove, the chance of cancer returning, scientists and doctors have not only to find these rare cells, but also treat them, Prof. Pan explains.

Nanotechnology 'works at scale of biology'

Nanotechnology is proving to be a very useful tool in medicine because it works at the scale at which "much of biology occurs."

It provides tools that are a million times smaller than an ant and can manipulate materials at the same level as the machinery of cells and even of their DNA. As an example, the diameter of a strand of DNA is roughly 2 nanometers.

A group of genes called "signal transducer and activator of transcription," or STAT genes, code for a group of cell proteins that, upon receiving certain signals, can enter the cell nucleus.

Once inside the cell nucleus, STAT proteins bind to certain parts of its DNA, where they set about switching other genes on and off.

STAT3 is a particular member of the STAT gene family that plays a role in many cell processes, including cell growth, division, movement, and self-destruction, or apoptosis.

Drug nanoparticles target cancer stem cells

In their study paper, Prof. Pan and his colleagues explain that cancer researchers are interested in STAT3 as a target for new treatments. They also note that there is evidence that STAT proteins have also been linked to breast cancer stem cells.

They go on to explain how they developed and tested a new way to "selectively target" cancer stem cells in treated tumors and switch off certain genes that are "downstream" of STAT3 to turn off their stemness.

The targeted delivery system comprised a niclosamide-laden nanoparticle that homed in on a protein called CD44 that uniquely sits on the surface of breast cancer stem cells.

After running some experiments on cultured cells and also in live mice, the team found that the drug-bearing nanoparticles deactivated STAT3, made the cancer stem cells lose their stemness, and significantly reduced their ability to make cancer come back and appear in other parts of the body — a process called metastasis.

They also found that growth of cancer cells reduced, both in the cultures and in the mice.

The team hopes that their novel approach will be accessible and inexpensive because it uses nanoparticles that are easy to make together with an already-approved drug.

"We purposely used an extremely inexpensive drug. It's generic and we can mass produce it on a very large scale. The nanoparticles are a polymer that we can make on a large scale — it's highly defined and consistent, so we know exactly what we are delivering. The rest of the process is just self-assembly."

Prof. Dipanjan Pan