Nanotherminators go out to fight cancer

Researchers at the University of North Carolina have developed and successfully tested on animals a new drug delivery system using biodegradable liquid metal to target cancer cells. 

According to the head of the study, Associate Professor Zhen Gu, the achievement of the work carried out is that the proposed technique is able to increase the effectiveness of the delivered drugs, help doctors determine the localization of the tumor, and the material necessary for its implementation can be produced in large batches and at the same time is completely biodegradable and very low-toxic. 

To create their so-called "nanotherminators", the authors place liquid metal (an alloy of gallium and indium) in a solution containing two types of molecules known as polymer ligands. After that, the solution is heated by ultrasound, which causes the liquid metal to explode with the formation of nanodrops with a diameter of about 11 nanometers. The ligands contained in the solution are attached to the surface of the droplets as they split off from the bulk of the liquid metal. At the same time, an "envelope" of oxidized metal is formed on the surface of the nanocapels. This oxidized shell, together with the ligands, prevents the reverse fusion of metal nanodrops.

After that, the antitumor drug doxorubicin is added to the solution. One of the types of ligands on the surface of nanocapsules absorbs doxorubicin and retains it. Such drug-loaded nanoparticles can be isolated from the solution and injected into the bloodstream.

 
On the left is a schematic image of liquid crystal "nanotherminators". The red spheres represent doxorubicin.
On the right is an image of nanocapels obtained using a transmission electron microscope.Ligands of the second type on the surface of nanocapsules effectively localize cancer cells and bind firmly to receptors on their surface.

After that, cancer cells absorb nanoparticles, the oxidized shell of which is destroyed by the action of an acidic intracellular environment, releasing ligands, which in turn release doxorubicin. 

At the same time, the nanocapsules released from the oxide shell and ligands merge into larger metal droplets that are easily detected using diagnostic methods, which can potentially help doctors in finding tumors.

As it reacts with the acidic environment inside the cancer cells, the liquid metal dissolves and releases gallium ions. Which seemed to increase the effectiveness of antitumor drugs, including the effectiveness of their effect on tumor cells resistant to traditional drugs.

This process ensures the gradual degradation of the metal, minimizing its long-term toxicity. Based on in vitro experiments, researchers suggest that in the conditions of the body, liquid metal completely degrades within a few days, passing into a form that the body absorbs and removes without any problems without registering side effects.

The developers tested the technique on a mouse model and demonstrated its significantly higher effectiveness in inhibiting the growth of malignant ovarian tumors compared to the effectiveness of the administration of the usual drug doxycycline. It is also important that monitoring the condition of animals for 90 days did not reveal signs of toxicity associated with the introduction of liquid metal.

The authors note that the work carried out is just an experimental verification of the concept, but its results are very promising. Like the Terminator that came from science fiction, liquid metal carriers are transformable: after separating from the bulk of the metal, they merge again inside cancer cells and eventually degrade and are excreted from the body. The developers hope that additional experiments on larger animal models will significantly bring potential clinical trials closer.

Article by Yue Lu et al. Transformable liquid-metal nanomedicine is published in the journal Nature Communications.

Evgeniya Ryabtseva

Portal "Eternal youth" http://vechnayamolodost.ru based on materials from North Carolina State University: Liquid Metal 'Nano-Terminators' Target Cancer Cells.