Bio-Nanocomposite Delivery System Attacks Cancer at the Cellular Level

The cancer cells have absorbed the packages and show signs they are about to die, even without the inclusion of the cytotoxin. The green spots show regions with high concentration of the bio-nanocomposite (b-NCP) packages. [Heloisa Bordallo and Murillo Martins, Niels Bohr Institute]

The most common treatments for cancer—radiation and chemotherapy—are unfortunately indiscriminate in their killing capacity, laying waste to healthy cells as well as cancerous ones. Moreover, their effectiveness is limited when the cancer has spread throughout the body, as the treatment preference only extends to rapidly dividing cells, which constitute cancer cells as well as a host of other healthy tissues.

Now, researchers from the Niels Bohr Institute at the University of Copenhagen have been developing a gentler treatment that causes cancer cells to absorb a cytotoxic Trojan horse, leading to their destruction and leaving healthy cells unaffected.

The investigators wanted to design and construct a nanoscale vehicle that could transport the cytotoxin directly to the cancer cells via the bloodstream and would prompt the cells to allow the payload in, so that the cancer cells were destroyed.

The first hurdle the scientists needed to overcome was creating the proper vehicle to transport the toxic cargo. The team looked to using tiny magnetic beads, a well-established approach in medical research, that could be injected directly into the bloodstream. By placing a magnet at the site of tumor, physicians can coax the beads to congregate to that position.

To the research team this seemed to be the most logical approach, which subsequently allowed them to focus their attention to creating the cytotoxic payload.   

“We designed a ring-shaped sac of a biologically useful base material, and using chemical processes we encapsulated the cytotoxin surrounding the beads. The coupling does not always happen, but using a separation process we can sort the beads from where the coupling with the sac did not succeed,” explained lead study author Murillo Martins, Ph.D., a postdoc in X-ray and neutron science at the Niels Bohr Institute.

After confirming that contents of the package contained the cytotoxin, the researchers looked to develop the final piece of their new drug delivery system—getting the package into the cell. Cells have surrounding membranes that protect them against foreign substances. However, they also have keyholes (receptors) that can open up if the cell wants to let a substances enter. Finding the substance that fits into the keyholes was the investigators' main goal.    

“I thought why do breast cancer, lung cancer, and ovarian cancer so often spread to the bones?” Dr. Martins inquired.  “Bones are composed of minerals like calcium phosphates. Do cancer cells need these substances to grow? Can these substances be used as doorways to the cell? I decided to investigate this.”

Dr. Martins and his colleagues made a coating of calcium phosphate on the package with the cytotoxin, and tested it to see if the payload would be absorbed by the cells. More importantly, which cells would it affect?

With the help of collaborators at the Laboratory of Tumor Immunology at the School of Bioscience in Botucatu, Brazil, the researchers tested their new concoction on breast cancer, lung cancer, and colon cancer cells, in addition to healthy cells (monocytes and fibroblasts)

The findings from this study were published recently in Scientific Reports in an article entitled “Restricted Mobility of Specific Functional Groups Reduces Anti-Cancer Drug Activity in Healthy Cells.”

The scientists described experimental results showing that the cancer cells absorbed the packages with the cytotoxin.

“We could see that the nanoparticles with the cytotoxin were absorbed by the cancer cells,” stated senior study author Heloisa Bordallo, Ph.D., associate professor in X-ray and neutron science at the Niels Bohr Institute. “This caused the metabolism of the cancer cells to change and the cells showed signs that they were about to die. The healthy cells, meanwhile, do not show any evidences of absorbing the packages with the cytotoxin. This suggests that the method can be used to send cytotoxin around the body with reduced toxicity and could therefore be potentially safer for healthy cells.”

The researchers were excited by their findings and are now looking to expand their studies to various other cancers and health tissues.