Attempting to attack cancer cells can be tricky, as it is difficult not to harm healthy cells in the process. Researchers have found a way to target diseased cells by taking advantage of an enzyme that is produced in large quantities by cancer cells, while leaving healthy cells alone. The enzyme attracts self-assembling molecules that form a hydrogel nanofiber web around the bone cancer cells, killing them. Ricardo Pires of the University of Minho in Portugal was lead author of the paper, published in the Journal of the American Chemical Society.
The idea for these self-assembling particles was conceived while considering the extracellular matrix that surrounds most cells, providing structural support, capturing nutrients, and even playing a role in cell-to-cell communication. Except instead of providing useful functions that are necessary for complex organisms such as we, the molecules designed by Pires’ lab are meant to function as a molecular death web, choking the life out of cancerous cells.
The molecules are a combination of hydrophilic glucosamine, a hydrophobic aromatic group, and phosphate. Osteosarcoma cells overexpress the enzyme alkaline phosphatase (ALP), which seeks to dephosphorylate the molecule. Once that phosphate is gone, the hydrophilic and hydrophobic ends are free to self-assemble, forming a cocoon-like hydrogel web around the cell. Once the molecules begin to assemble, it takes about seven hours before the metabolic activity of the cancer cell is impacted, and in 24 hours, the cell is dead.
Image credit: Pires et al., 2014
During the study, the molecules were added to a solution containing osteosarcoma cells and healthy cartilage cells, which generate about 18 times less ALP. Ultimately, the molecules were able to kill 95% of the cancer cells, and only 15% of the cartilage cells. Microscopic inspection of the dead cells revealed that the molecules had encapsulated the cell. The exact mechanism that caused the cellular death has not been verified, but it is suspected to be because the hydrogel web prevents the cell from taking in nutrients, while simultaneously sealing in waste products.
Many different approaches have been taken in order to produce self-assembling molecules that target cancer cells, though previous studies have relied on hydrophilic and hydrophobic peptides, rather than carbohydrates like shown in the current study.
Of course, this method is more or less proof of concept and requires significantly more work before it can be anticipated as an actual treatment. It was shown to work for cells in solution, and they are dependent on environmental factors such as pH and temperature. However, behavior in a tissue sample or whole organism is considerably different. The amount of molecules needed to kill the cancer cell is currently extremely high, which could cause side effects in healthy cells that produce large amounts of ALP, including those in liver and kidney tissue.
[Hat tip: Chemical & Engineering News, ACS]