Brazilian scientists described a new strategy of combat against bacteria resistant to antibiotics in the magazine Scientific Reports, belonging to the Springer Nature.
The method described consists of coated nanoparticles made of silver and silica - potentially toxic for microorganisms, but also for human cells - with a layer of antibiotic. Thus, chemical affinity, the nanofarmaco acts only on pathogens, i.e.: becomes inert for the organism.
"We use the antibiotic as a kind of bait. In this way, we were able to transport the nanoparticle to the bacterium with a large amount of the drug. The combined action of the drug with the silver ions was capable of killing even the resistant organisms, "said Mateus Borba Cardoso, scientist at the National Center for research in energy and materials (CNPEM).
This work, which had the support of FAPESP, is part of a line of research whose objective aims to develop systems that make selective action of nanoparticles.
In previous articles, the Group showed that this strategy can be viable for the treatment of cancer, through transport of the chemotherapeutic drug to tumor cells with preservation of healthy cells (agencia.fapesp.br/23210). You can also try it in the inactivation of the HIV virus, which causes AIDS, in bags of blood for transfusion, for example (agencia.fapesp.br/23902).
"There are commercial medications that contain nanoparticles and, in general, serve to cover the active principle and extend the time of life within the body." But our approach is different. We decorate the surface of the nanoparticle with certain chemical groups that serve to direct it to the place where it must act in a selective way", said Borba Cardoso.
In the most recent article, the group describes the synthesis of nanoparticles formed by a nucleus of silver coated by a layer of porous silica for the purpose of allowing the passage of ions. On the surface were placed several molecules of the antibiotic ampicillin in a system that, according to Borba Cardoso, not arranged randomly.
"Using molecular modeling, we determine which part of the molecule of ampicillin interacts better with the bacterial membrane. We leave then all molecules of the drug with the key side facing the outer side of the nanoparticle, thus increasing the possibilities of interaction with the pathogen", explained.
Molecular modeling work counted with the collaboration of Hubert Karl Stassen, of the Institute of chemistry of the Federal University of Rio Grande do Sul (UFRGS).
The effect of the nanoantibiotico in comparison with the conventional ampicillin was analyzed in two lineages other than the bacterium Escherichia coli, which integrates the intestinal flora of the mammals and, in certain situations, can cause food poisoning.
In the susceptible lineage to ampicillin, died virtually 100% of microorganisms with the conventional drug both version combined with silver. However, in the resistant line, only the nanoantibiotico was effective.
The next step consisted of testing the effect of a lineage of human kidney cells. While the nanoparticle silver and silica uncoated ampicillin was extremely toxic, conventional ampicillin and combined with silver version were also safe.
"Confocal microscopy images show that, apart from not being toxic, Nanoparticle coated with ampicillin does not interfere on the cell cycle. Phases of mitosis continues its course without any change,"said Borba Cardoso.
In the opinion of the investigator, the same strategy could be used in combat against other bacterial species that developed resistance to antibiotics. It is also possible to vary the medication used in the surface of the nanoparticle, to treat different kinds of infections.
However, this system has a disadvantage: silver and silica are inorganic materials, nanoparticles are not metabolized, and tend to accumulate in the body.
"We don't know yet where this buildup there would be and what would be the effects. To find out, it will be necessary to do tests on animals. "Anyway, continue to refine the system in such a way make it more safe", said Borba Cardoso.
One of the possibilities is to put, instead of silver, a second antibiotic of different spectrum in the nucleus. And another option would be to develop a nanoparticle that is small enough to be excreted through the urine.
In any case, according to Borba Cardoso, the nanoantibiotico in its current form could be used in the treatment of extreme cases, such as patients with hospital-acquired infections that do not respond to conventional antibiotics.
"The possible accumulation of nanoparticles in the body, in such cases, would be a small price that would have to pay to avoid death," he said. The Group of scientists is doomed now looking for partners to carry out the tests in animals. (Source: Agency FAPESP/DICYT)