Molecules branched-polymer surfaces capture tumour cells in blood

Molecules on branched-polymer surfaces capture tumour cells in blood

12:45 AM, 18th November 2011
Molecules on branched-polymer surfaces capture tumour cells in blood


ILLINOIS, US: The removal of rare tumour cells circulating in blood might be possible with use of biomolecules bound to dendrimers, highly branched synthetic polymers, which could efficiently sift and capture diseased cells, according to new research at University of Illinois, 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 tumour cells by biomimicry - using nanotechnology to create artificial surfaces. “We want to take advantage of what nature gives us. We want to create new biomimetic surfaces that will allow us to remove damaged cells from blood,” said Seungpyo Hong, Assistant Professor of Biopharmaceutical Sciences at UIC.

Hong, Lead Researcher of the study and his coworkers created a highly sensitive surface that enables multivalent binding. The biomimetic surface was created using dendrimers of seventh-generation polyamidoamine (PAMAM) and anti-epithelial cell adhesion molecule (aEpCAM).

In the body, cancer cells can detach from a primary tumour and flow throughout the bloodstream, enabling them to seed distant new tumours. Rare and difficult to capture, only a few circulating tumour cells can be found in a millilitre 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 tumour cell models, with each used to compare the cell adhesion of dendrimer surfaces to a linear polymer of polyethylene glycol (PEG). Nano-scale PAMAM dendrimers were chosen because they enabled multivalent binding, along with physiological process of “cell rolling” induced by E-selectin, which mimics the process by which circulating tumour cells are recruited to the endothelia and enhances surface sensitivity toward tumour cells, said Hong.

The surface developed by 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 aEpCAM-coated PEG surface that is current gold standard for circulating tumour cell detection. Hong said this is the first study to capture tumour cells on surface exploiting multivalent effect, which is most likely due to spherical architecture of dendrimers. The research was selected as a “Hot Paper” by Angewandte Chemie journal.

The results demonstrate that the combination of nanotechnology and biomimicry has a “Great potential to be applied for highly sensitive detection of rare tumour cells from blood,” said Hong.

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 National Science Foundation.

(C) University of Illinois News




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