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An effective weapon to fight cancer - antibodies

Engineers propose novel approach to antibody-based imaging of cancer cells using ultra-tiny silica nanoparticles known as 'Cornell dots'

Illustration of a primary Cornell spot (left) attached to an antibody fragment (center) while binding to the HER2 cancer cell receptor (right). The dot and the antibody attached to it together are less than 8 nanometers in diameter, the size threshold for removal from the body by the kidneys.
Illustration of a primary Cornell spot (left) attached to an antibody fragment (center) while binding to the HER2 cancer cell receptor (right). The dot and the antibody attached to it together are less than 8 nanometers in diameter, the size threshold for removal from the body by the kidneys.

[Translation by Dr. Nachmani Moshe]

Engineers are now proposing an innovative approach to antibody-based imaging of cancer cells, using ultra-tiny silica nanoparticles. Antibody-based imaging of a particularly aggressive form of breast cancer has been clinically tested around the world, but the road from the experimental phase to the application phase has encountered a serious trade-off: safety. The concern stems from an ineffective focus on the tumor, which may cause the accumulation of the active radioactive material in the bone marrow, liver and kidneys. Recent research efforts focus on nanoscale carriers attached to components of the immune system, however these carriers are generally still too large (20 nanometers) to be removed quickly from the body after the imaging stage.

Cornell University engineering professor Ulrich Wiesner, along with partners from other research centers in the US, proposed a new approach that makes use of ultra-tiny silica nanoparticles, known as 'Cornell dots', which were developed in his laboratory over a dozen years ago. The researchers attached antibody segments to these points so that the result was carriers smaller than 8 nanometers in diameter, a characteristic that allows the removal of the contrast agent while obtaining the selectivity required for effective imaging of cancer tumors. The research findings have long been published in the prestigious journal Nature Communications. The lead researcher says that this study creates a "completely new route" for the use of antibody segments for the treatment of several diseases, especially cancer, and for diagnosis as well as drug delivery, a new research field known as 'theranostics'.

"This is the first time we have tested these antibody segments," explains the lead researcher, "while harnessing the power of the antibodies in the fight against cancer." 'Cornell points' and their new generation 'primary Cornell points', have been improved since their development in 2005, and it became clear that they are safe for use in the human body as of 2014. Two years ago, the points showed that they not only have the ability to locate cancer cells, but that they themselves have the ability to heal which results in the killing of the cells. This updated research allows the dots to function not only as cancer detectors but also as tumor detectors with the help of the antibody segments. The researchers use a defined segment of the Y-shaped antibody, as opposed to the complete antibody, with the aim of maintaining a size and molecular weight that will allow efficient removal from the body.

The researchers' target was HER2-positive breast cancer, which is more aggressive and deadly than HER2-negative breast cancer. As part of their research, the scientists attached an antibody fragment specific to the HER2 protein in a binding site that does not interfere with its biochemical activity. At the same time, the other research partners attached the segment to the surface of the Cornell dots in order to maintain a total diameter of less than 8 nanometers. Both plate experiments and live experiments (mouse) were able to focus on HER2-positive breast cancer cells, when the accumulation in the cells was about 20 percent higher than previous results. "The injected substance flows through the blood system, has to leave the blood vessels, has to flutter through connective tissue, has to bind to the tumor and then penetrate into the core of the tumor," explains the main researcher. "We are interested in getting 100% of accumulation at the target site, that is, the tumor, but when considering all the other bumps in the way of the therapeutic substance in the human body, the value of 17% is not small." "The findings of this study are particularly fascinating," says one of the researchers, "since they suggest that we can selectively deliver a variety of small therapeutic molecules - for chemotherapy, inhibitors and radiotherapy - without the toxicity that is usually present in larger carriers."

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