Molecules on branched-polymer surfaces can capture rare tumor cells in blood

November 17, 2011

The removal of rare tumor cells circulating in the blood might be possible with the use of biomolecules bound to dendrimers, highly branched synthetic polymers, which could efficiently sift and capture the diseased cells, according to new research at the University of Illinois at Chicago.

Dendrimers have been used to encapsulate drug molecules and serve as a delivery vehicle, but in the new study they were employed to capture circulating tumor cells by biomimicry -- using nanotechnology to create artificial surfaces much like those in real cells.

"We want to take advantage of what nature gives us," says Seungpyo Hong, lead researcher of the study, published in the journal Angewandte Chemie. "We want to create new biomimetic surfaces that will allow us to remove damaged cells from the blood."

Hong, assistant professor of biopharmaceutical sciences at UIC, and his coworkers created a highly sensitive surface that enables multivalent binding -- the simultaneous binding of many molecules to multiple receptors in a biological system. The biomimetic surface was created using dendrimers of seventh-generation polyamidoamine, or PAMAM, and the anti-epithelial cell adhesion molecule, or aEpCAM.

In the body, cancer cells can detach from a primary tumor and flow throughout the bloodstream, enabling them to seed distant new tumors. Rare and difficult to capture, only a few circulating tumor cells can be found in a milliliter of blood in a cancer patient. By comparison, the same volume of blood contains several million white blood cells and a billion red blood cells, Hong said.

Three breast cancer cell lines were used as circulating tumor cell models, with each used to compare the cell adhesion of the dendrimer surfaces to a linear polymer of polyethylene glycol. PEG is commonly used to bind molecules to improve the safety and efficiency of therapeutics.

The nano-scale PAMAM dendrimers were chosen because their size and surface dimension could accommodate multiple anti-epithelial cell adhesion molecules, Hong said. This enabled the multivalent binding, along with the physiological process of "cell rolling" induced by E-selectin, which mimics the process by which circulating tumor cells are recruited to the endothelia and enhances the surface sensitivity toward tumor cells.

The surface developed by the UIC research team demonstrated up to a million-fold increase in binding strength, and up to 7-fold increase in detection efficiency, as compared to the aEpCAM-coated PEG surface that is the current gold standard for circulating tumor cell detection.

Hong says this is the first study to capture the tumor cells on the surface exploiting the multivalent effect, which is most likely due to the spherical architecture of dendrimers. The research was selected as a "Hot Paper" by Angewandte Chemie and highlighted in Faculty of 1000 by Donald Tomalia, the inventor of PAMAM dendrimers.

The results demonstrate that the combination of nanotechnology and biomimicry has a "great potential to be applied for highly sensitive detection of rare tumor cells from blood," Hong said.
-end-
Co-authors are David Eddington, associate professor of bioengineering at UIC; and research assistants Ja Hye Myung, Khyati Gajjar and Jelena Saric. The research was funded through a grant from the National Science Foundation.

University of Illinois at Chicago

Related Tumor Cells Articles from Brightsurf:

A more sensitive way to detect circulating tumor cells
Breast cancer is the most frequently diagnosed cancer in women, and metastasis from the breast to other areas of the body is the leading cause of death in these patients.

Cancer researchers train white blood cells to attacks tumor cells
Scientists at the National Center for Tumor Diseases Dresden (NCT/UCC) and Dresden University Medicine, together with an international team of researchers, were able to demonstrate that certain white blood cells, so-called neutrophil granulocytes, can potentially - after completing a special training program -- be utilized for the treatment of tumors.

How to prevent the spread of tumor cells via the lymph vessels
Scientists from the German Cancer Research Center and the Mannheim Medical Faculty of the University of Heidelberg identified a new way to block the dangerous spread of tumor cells via lymphatic vessels.

The CNIO reprograms CRISPR system in mice to eliminate tumor cells without affecting healthy cells
CNIO researchers destroyed Ewing's sarcoma and chronic myeloid leukaemia tumor cells by using CRISPR to cut out the fusion genes that cause them.

Feeding off fusion or the immortalization of tumor cells
Despite all recent progress, cancer remains one of the deadliest human diseases.

How do tumor cells divide in the crowd?
Scientists led by Dr. Elisabeth Fischer-Friedrich, group leader at the Excellence Cluster Physics of Life (PoL) and the Biotechnology Center TU Dresden (BIOTEC) studied how cancer cells are able to divide in a crowded tumor tissue and connected it to the hallmark of cancer progression and metastasis, the epithelial-mesenchymal transition (EMT).

How tumor cells evade the immune defense
Scientists are increasingly trying to use the body's own immune system to fight cancer.

Engineered immune cells recognize, attack human and mouse solid-tumor cancer cells
CAR-T therapy has been used successfully in patients with blood cancers such as lymphoma and leukemia.

New pathway to attack tumor cells identified
A study led by the Institut de Neurociències (INc-UAB) describes a new strategy to tackle cancer, based on inducing a potent stress in tumor causing cell destruction by autophagy.

Nutrient deficiency in tumor cells attracts cells that suppress the immune system
A study led by IDIBELL researchers and published this week in the American journal PNAS shows that, by depriving tumor cells of glucose, they release a large number of signaling molecules.

Read More: Tumor Cells News and Tumor Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.