Drug-delivering Nanoparticles Destroy Elusive Cancer Stem Cells

Tiny drug-laden nanoparticles that seek and destroy cancer stem cells have been designed by University of Illinois researchers.

A study led by Dipanjan Pan, an Illinois professor of bioengineering, developed nanoparticles that specifically bind to a protein that marks the surface of breast cancer stem cells. Cancer stem cells are elusive and rare cells that can cause cancer to come back even when years have passed since the initial tumor was treated.

Encapsulated in the particles is the drug niclosamide – a drug commonly prescribed around the world to treat tapeworm infections, but in cancer stem cells it turns off key gene pathways that give the cells the stemlike properties that enable them to grow and spread.

“It is critical to administer treatments for already-developed tumors; however, long-term survival and not allowing it to come back are equally important. We want to destroy the cells that are hidden in the tissue and cause the cancer to come back or spread to other parts of the body,”

Pan said.

GPS-enabled Nanoparticles

Cancer stem cells represent a tiny fraction of cells in a tumor, but it only takes one or two to seed a new tumor, Pan said. The challenge for physicians and researchers is not only finding these cells, but treating them.

Pan’s group created nanoparticles that target a protein called CD44, which only appears on the surface of cancer stem cells, and tested them on breast cancer tumors in cell cultures and in live mice.

“I call them ‘GPS-enabled nanoparticles,’ because they seek out only the cells that have cancer stem cell properties. Then they latch onto the cells and deliver the drug. To the best of our knowledge, this is the first demonstration of delivering cancer stem-cell-targeted therapy with a nanoparticle,”

said Pan, who is also a faculty member of the Carle Illinois College of Medicine and the Beckman Institute for Advanced Science and Technology.

The researchers used the nanoparticles to deliver niclosamide, which is on the World Health Organization’s List of Essential Medicines, an index of the safest and most effective drugs in the world. Pan’s group previously found that niclosamide works on a particular gene-regulation pathway in cancer stem cells.

Niclosamide

In the new study, the cancer stem cells lost their stemlike properties after treatment with the niclosamide-bearing targeted nanoparticles, making them less able to cause the cancer to recur or metastasize. The researchers also saw a significant decrease in overall cancer cell growth, both in the cell cultures and in the mice.

By using an already-approved drug and easy-to-manufacture nanoparticles, Pan hopes that this system can become an accessible and cost-efficient treatment to prevent cancer recurrence in patients

“We purposely used an extremely inexpensive drug. It’s generic and we can mass produce it on a very large scale,” Pan said. “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.”

The researchers are working to create a combination therapy that can deliver drugs for the primary cancer, such as traditional chemotherapies, as well as targeted agents that can treat cancer stem cells. They are also testing the nanoparticle drug-delivery system in large animal models to bring it a step closer to the clinic.

Santosh K Misra, Arun De and Dipanjan Pan
Targeted Delivery of STAT-3 Modulator to Breast Cancer Stem Like Cells Down-regulates a Series of Stem-ness Genes
Mol Cancer Ther November 14 2017 DOI: 10.1158/1535-7163.MCT-17-0070

Image: nanoparticles target cancer stem cells (yellow), the rare cells within a tumor (blue) that can cause cancer to recur or spread. Credit: Dipanjan Pan