Aptamers as means of precise drug delivery to tumors
Detecting and treating a tumor without damaging healthy tissues is a very difficult task, and the most effective therapeutic approaches are often invasive and very difficult to tolerate by the body.
Scientists at Duke University (Durham, North Carolina), working under the leadership of Bryan Clary, have developed a method for delivering antitumor agents directly to the tumor area using special aptamer molecules that specifically bind to tumor tissue.
Aptamers are small fragments of RNA that bind to a specific target molecule (usually a protein). These compounds are very easy to synthesize; in addition, they are well amenable to modification, which allows for higher stability compared to other means of targeted delivery, such as antibodies of a protein nature. An important parameter is also the low probability of recognition of aptamers by the immune system, which makes them promising candidates for use in the diagnosis and treatment of tumors.
According to the first author of the article, Jing Mi, the most important point is that when using aptamers, it is not necessary to obtain exhaustive information about changes in the protein composition of the tissue associated with the disease, which greatly facilitates the process of developing a molecular carrier. Those aptamers that will show the best ability to bind to tumor cells and will not attach to healthy cells can be used even if their target is proteins whose connection with the disease has not yet been detected.
As part of their work, the authors injected a mixture of various fragments of RNA chains into mice with liver tumors belonging to the type of secondary tumors formed during metastasis of colon cancer. They assumed that RNA molecules binding to normal cellular elements would be eliminated from the body, which happened in practice. As a result, the researchers obtained fragments of RNA specific to tumor proteins. They removed the tumors, extracted the RNA bound to its proteins, amplified them and injected them again into the animals in order to identify fragments that bind most strongly to target proteins. As a result of a 14-fold repetition of this process, the researchers isolated an aptamer that specifically binds to the enzyme RNA helicase p68, a nuclear protein synthesized by colon cancer cells.
(The figure on the left shows the secondary structure of the aptamer optimally binding to the target protein, on the right – one of the rejected options. The different sections of the molecules are outlined with a dotted line.)
The results of the work are published in the preliminary on-line version of Nature Chemical Biology in the article "In vivo selection of tumor-targeting RNA motifs".
The authors claim that the described process can be repeated for almost any type of cancer, as well as for other diseases. At the same time, repeating the process with the same type of liver tumor may lead to the identification of aptamers specific to other tumor proteins. The authors note that in their work they purposefully searched for an aptamer to the p68 protein, the overexpression of which is characteristic of colon cancer.
Currently, researchers are already studying the possibilities of attaching antitumor drugs to aptamers, after which they will test the effectiveness of delivering aptamer-drug complexes to tumors.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on Science Daily: First Live Targeting of Tumors With RNA-Based Technology02.12.2009