Nanocubes squeeze drugs into the tumor
The new targeted drug delivery system confirms its effectiveness
Nanonewsnet based on Vanderbilt University materials: Nanosponge drug delivery system more effective than direct injectionA targeted delivery system loaded with an anti-cancer drug, based on a new material called a nanowell, delays the growth of a cancerous tumor three to five times more effectively than conventional injections.
This conclusion was reached by scientists from Vanderbilt University (Vanderbilt University). They report on the results of their work in an article published in the journal Cancer Research (Ralph J. Passarella et al. Targeted Nanoparticles That Deliver a Sustained, Specific Release of Paclitaxel to Irradiated Tumors).
"Effective targeted drug delivery systems have long been a dream, but this dream is largely not being realized due to the complex chemistry involved in such systems," says Eva Harth, associate professor of chemistry at Vanderbilt University, who developed a delivery system using a nanowell. "We have made a significant step forward in overcoming these obstacles."
The Hart Laboratory conducted its research in collaboration with the laboratory of Dennis E. Hallahan, a former professor of radiation oncology at Vanderbilt University and now a professor at the University of Washington School of Medicine (Washington University).
To understand how the delivery system developed by Hart works, imagine tiny, virus-sized, drug-filled sponges to which special chemical linkers are attached, mainly binding to structures located only on the surface of tumor cells. Such sponges are injected into the body by injection. They circulate in the body with the blood flow until they meet with a cancer cell. As a result, they either "stick" to its surface, or are absorbed into the cell, starting to release their cargo in a controlled and predictable manner.
Illustration of a nanowell particle.
The red ovals represent the cargo of the drug.
Peptides binding the nanocube to the tumor surface,
shown as conditional chemical symbols
Address delivery systems of this type have several main advantages: since the drug is released only near the tumor and does not circulate throughout the body, this dose becomes more effective. There are also fewer side effects, as there are fewer toxic drugs in direct contact with healthy tissues.
"We called our material a nanowell, but in fact it looks more like a three–dimensional network," says Hart. "It is based on long chains of polyester. We mix such chains in solution with small molecules called cross-linkers, which act as tiny hooks that hold together different parts of the polymer."
Eventually, spherical particles are formed with an internal cavity in which the molecules of the medicinal substance can be placed. Polyester is a biodegradable polymer and gradually breaks down in the body. As this happens, the drug contained in the particle is released from it in a completely predictable way.
"Predictable drug release is one of the main advantages of this delivery system compared to other systems currently being developed that deliver drugs using nanoparticles," says Hart.
When nanoparticles reach their target, many systems release their cargo quickly and uncontrollably. This is called an explosive effect, and in this case it is difficult to determine the effective doses of the drug.
Another important advantage is that sponge nanoparticles are water-soluble. Encapsulation of anticancer drugs in the nanowell structure allows the use of poorly soluble hydrophobic drugs. Currently, such drugs need to be mixed with other chemicals called adjuvants, which reduces the effectiveness of the drug itself and can lead to adverse side effects.
In addition, the size of sponge nanoparticles can be controlled. By changing the ratio of cross-linkers and polymer, you can make the particles larger or smaller. This is important because the study showed that targeted delivery systems work most efficiently if the particles are smaller than 100 nanometers. The particles used in this study were 50 nanometers in size.
"The relationship between particle size and the efficiency of our delivery system is a subject of active study," says Hart.
Another advantage of the Hart system is its chemical simplicity. Researchers have developed simple and effective methods for obtaining nanoparticles and binding linkers to them, which are peptides, relatively small biological molecules consisting of amino acids.
"Many other drug delivery systems require the use of complex chemicals, which makes it difficult to produce them on an industrial scale, and we have always had this in mind," Hart emphasizes.
Nanohub fixed on human breast tumor cells.
Peptide linkers are shown as two groups of balls
(in fact, there are about 30 peptides on the surface of the nanoparticle).
The peptide ligand used in animal experiments was developed in Hallahan's laboratory, where the effectiveness of the entire system was also tested on tumors in mice. The peptide used in this study selectively binds to tumors exposed to radiation.
The drug used in animal experiments was paclitaxel (Taxol), used in cancer chemotherapy. Scientists have recorded the reaction of two different types of tumors – a slow-growing human breast tumor and a rapidly developing mouse glioma – to a single injection. In both cases, they found that it increases the death of cancer cells and delays tumor growth, "surpassing the effectiveness of known chemotherapeutic approaches."
The next step in the research will be to conduct experiments with repeated injections in order to make sure whether it is possible to completely stop the growth of the tumor with the help of a nanowell and reverse it. Hart is also going to conduct a more complete toxicological examination of his system, which is required before clinical trials.
Portal "Eternal youth" http://vechnayamolodost.ru08.06.2010