Stealth nanoparticles with an anti-cancer warhead
New nanoparticles suppress the ability of tumors to resist chemotherapy
NanoNewsNet based on ACS News: Stealth nanoparticles lower drug-resistant tumors’ defensesSome of the most dangerous types of cancer are those that are able to "outwit" the drugs developed to combat them.
Scientists who published an article in the journal ACS Nano (Layer-by-Layer Nanoparticles for Systematic Codelivery of an Anticancer Drug and siRNA for Potential Triple-Negative Breast Cancer Treatment) focused their attention on a type of breast cancer that is highly resistant to modern drugs. They have developed a new type of "Trojan horse" – a system for delivering tiny particles to tumor cells that reduce the ability of cells to defend themselves and increase the effectiveness of treatment with standard chemotherapeutic agents.
Triple negative breast cancer is an aggressive disease that is difficult to treat with standard drugs, with a poor prognosis for patients. Cells of this type of cancer resist drugs by increasing the synthesis of certain proteins that protect tumors from chemotherapeutic drugs. Intervention in this process may give antitumor agents a better chance of suppressing the development of a resistant tumor.
Recently intensively studied molecules called small interfering RNAs, or miRNAs, open the way to the development of new cancer treatments. They can stop the synthesis of certain proteins and therefore are ideal candidates for the role of drugs that reduce the level of protective molecules synthesized by tumor cells. But the use of miRNA as part of anti–cancer therapy is associated with certain difficulties, and Paula Hammond and her colleagues from the Koch Institute of Integrative Cancer Research at the Massachusetts Institute of Technology decided to resort to new molecular engineering approaches.
They have developed a two-stage "stealth" drug delivery system that attacks triple negative breast cancer cells in human "stand–in" mice, often used in scientific research. Scientists have created "layered" nanoparticles, the components of which are assembled in a certain order around a nanoscale nucleus-a liposome. The antitumor drug is loaded into the nucleus of the particle, which is then covered with layers of negatively charged miRNAs alternating with layers of positively charged polypeptides (poly-L-arginine). A single bilayer of nanoparticles can be efficiently loaded with 3,500 miRNA molecules. After that, the entire particle is dressed in an outer shell – a layer invisible to the immune system that prevents the destruction of particles. Preserved in the blood serum for a long enough time (up to 28 hours), such nanoparticles more successfully cope with their therapeutic task. In addition, the outer layer allows the particles to bind specifically to tumor cells. All components of multilayer nanoparticles are biocompatible, biodegradable and non-toxic to the body.
The liposomal core of the nanoparticle contains the anti-cancer drug doxorubicin (or other drugs);
the outer layer consists of molecules that provide a "stealth" effect and binding of nanoparticles to cancer cells;
The inner layer is miRNAs that block the molecular pathway of the synthesis of protective proteins (Fig. ACS).In experiments on mice, targeted nanoparticles reached the tumor and reduced the levels of protective proteins by almost 80 percent.
In conditions of increased vulnerability of cancer cells, the anti-cancer drug loaded into nanoparticles showed a significantly higher therapeutic effect, which allowed to reduce the size of tumors by 8 times.
According to the authors, in general, these results prove the possibility of developing a new strategy for the treatment of aggressive recurrent triple negative breast cancer. In addition, this platform can be adapted to develop a wide range of controlled treatments customized for a specific type of cancer, using multiple drugs in a single delivery system based on nanoparticles.
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