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Use two keys

To direct substances to their purpose within the body, a delicate balance must be reached between stability and solubility

Courtesy of the researchers
Courtesy of the researchers

From a pill against a temporary headache to serious illnesses - the medicines have improved our lives beyond recognition. However, many of the drugs are distributed throughout the body's tissues, and therefore come with a price tag in the form of side effects. Sometimes, the side effects are so serious that they pose a danger to the patients to a degree comparable to the disease they want to cure. The nano revolution makes it possible to develop nano systems for carrying the drug molecules in our body (Drug delivery system), so that they are not released in the blood circulation and healthy tissues, but only in the target area, for example in the cancer tumor.

However, the great promise of selective drugs runs into one fundamental problem: if the nanosystems that carry the drug in our bodies are too stable, they may not break down when they reach their destination. Alternatively, if they are not stable enough, they may spill their contents elsewhere - and again produce side effects. Prof. Roi Amir from the School of Chemistry at Tel Aviv University is trying to solve this problem by building smart nano-systems to carry the drugs.

"The question is how to prepare polymer-based nanocarriers that will respond to a number of stimuli in their environment," says Prof. Amir, "and as a result gain better control over the release of the active substances, for example in the human body. Previously we studied the architecture of the structures, and our idea was to adapt the nanocarrier to a certain enzyme in the body. In this way, the nanocarrier travels throughout the body but only the enzyme in the target area breaks it down. For example, if there is internal bleeding in the stomach, it means that there are proteins that are expressed more in the damaged tissue - and the polymer nanocarrier is built so that it is sensitive to enzymes in the bleeding area."

But in the four years that have passed since the development of the smart nanocarriers, it turned out that they are not efficient enough. "For it to be broken down by the enzyme, the carrier has to be less stable than we would like to ensure that the drugs are not completely released in healthy tissues. In our current research, which won a grant from the National Science Foundation, we are perfecting the molecular structure of the nanocarrier, and trying to adapt several reaction mechanisms to the polymers that make up the carrier itself. In this way, we hope to develop carriers that will be both more stable and easier to disassemble."

The solution found is a safety mechanism, or a two-stage operating system. "Instead of adapting the entire nanocarrier to a certain enzyme, we adapt the polymers inside the nanocarrier to a number of different stimuli. In fact, there are two keys: the first stimulus makes the nanocarrier a little less stable, and thus sensitive to the second stimulus, but only when the nanocarrier comes into contact with the second stimulus does it break down completely and release its charge. Moreover, the nanocarrier is not at all sensitive to the second stimulus until it receives the first. We believe that in this way we can, on the one hand, increase stability and, on the other hand, achieve a much higher selectivity."

Prof. Amir believes that stable and selective nanocarriers may have many and varied practical consequences. "I, as a chemist," he says, "plan the general form and reaction mechanisms, that is, match the substance to the stimulus, in this case to the enzyme. On loan, I plan the vehicles. Later they will attach skis to travel on snow or floats to sail on water. The important thing for us is the general operating principle of these systems, and the ability to train for different stimuli. There is no doubt that an effective application of smart nanocarriers will be in the field of advanced medicine, but in the past there were already agricultural companies that expressed interest in research. The problem with medicines for humans and substances for plant protection is the same problem: they are not selective enough, and it is necessary to improve their effectiveness."

Life itself:

"I used to be a bartender. When I first came to the chemistry school, as a student, I was used to mixing new mixtures - and now we are creating new materials as well as training the future generation of scientists."

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