In trying to improve treatment options, developers of cancer therapies encounter hurdles such as making drugs highly specific and also delivering them to cancer cells. A new delivery method of a highly specific anti-cancer drug appears to have overcome some of these challenges in new work on cancer cell lines.
Researchers at Northwestern University have developed star-shaped nanoparticles coated with short segments of DNA that specifically target cancer cells, thus treating the tumor with the promise of not targeting other cells.
In a paper published in the American Chemical Society’s journal ACS Nano, the researchers detailed their work, from generating the nanoparticles and coating them with their designer drug, to observing the effects of their delivery in cancer cells.
Led by Teri Odom, professor of chemistry and material science and engineering at Northwestern University, the group utilized a DNA aptamer as their drug. This short segment of DNA carriers a specific sequence that is recognized by nucleoin — a protein that can be found on the surface of cancer cells more than most other types of cells.
Nucleoin is typically found within the cell, but cancer cells overexpress nucleoin, producing so much that some of the nucleolin moves to the external surface of the cell. The aptamer used in this study had already been demonstrated to bind quite strongly to nucleolin on the surface of cancer cells. Tightly bound, the aptamer and nucleolin make their way into the nucleus, causing the cell to kill itself off in a programmed set of processes called apoptosis.
In this study, the researchers were able to use transmission electron microscopy to observe how the treatment affected HeLa cells, a commonly used cancer cell line with an extensive history here at Hopkins. This allowed them to see in great detail the changes that cells and their nuclei underwent as they were dying.
Key to getting the drug to these cells is a delivery mechanism, which was where the nanoparticles came into the picture. Odom explained that a big advantage of their nanoparticles was the use of the HEPES buffer, commonly used in culturing cells, in the reaction to generate the biocompatible nanostars.
“This synthesis does not require cytotoxic surfactants that are typically used in the synthesis of anisotropically shaped gold nanoparticles,” Odom wrote in an email to The News-Letter.
Because of the interaction with nucleolin, the nanoparticles themselves do not need to enter the cell, allowing for flexibility in their size. The nanoparticles just need to reach the exterior of the cancer cells while carrying the tightly bound drug. The next trick was to get the drugs off of
the particles so they could successfully enter the cell by hitching a ride on the nucleolin proteins.
To do this, Odom and her group used high-intensity light pulses with a wavelength of around 700 nanometers, in the near infrared spectrum, releasing the drug from the particles. Accoding to Odom, the star-based shape of the particles was critical for the nanoparticles to effectively absorb this wavelength, which is within the biologically transparent window of 650 to 900 nanometers.
“This absorption peak is difficult to achieve with spherical particles of a similar size,” Odom wrote. She also added that light pulses within the biologically transparent window ensured that the light can penetrate the skin in the millimeter to centimeter range without causing damage. While the light is intense, Odom explained that the beam pulses used are so short that one would not feel anything if they had put their hand in the way.
“The exposure times needed to release the aptamers only lasts a few seconds,” Odom wrote.
As a control, the researchers utilized aptamers that contained an innocuous sequence not recognized by nucleolin. Agreeing with expectations, the cancer cells remained intact when exposed to these aptamer sequences.
Since submitting their paper, the researchers also explored the treatment in a dozen other cancer cell lines, finding similar results and responses to the treatment. According to Odom, testing other cell lines ensured that the effects were not specific for the HeLa line. Their next steps include testing non-cancerous cells.
“In addition, we are also testing other healthy cells such as fibroblast from skin and lung to ensure that healthy cells will not experience adverse effects,” Odom wrote.
According to Odom, the scientists are planning to test the system in mice. While their study had promising results, Odom cautioned that an actual treatment based on this system will take many years before full development and approval.
