Drug Development
Iron-based nanoparticle eliminates tuberculosis in mice, paving the way for new treatments
Unesp research shows a cheap and easily produced substance eliminated pulmonary infection after 30 days; the compound has the potential to reduce treatment time and toxicity.
Drug Development
Iron-based nanoparticle eliminates tuberculosis in mice, paving the way for new treatments
Unesp research shows a cheap and easily produced substance eliminated pulmonary infection after 30 days; the compound has the potential to reduce treatment time and toxicity.
Culture of Mycobacterium tuberculosis: The World Health Organization estimates that without treatment, the mortality rate from tuberculosis can reach 50%; when treatment is followed correctly, about 85% of patients recover (image: CDC/Wikimedia Commons)
Fernanda Bassette | Agência FAPESP – A compound based on iron encapsulated in lipid nanoparticles was able to completely eliminate tuberculosis in the lungs of mice after 30 days of treatment, according to a study by the Tuberculosis Research Laboratory of the Faculty of Pharmaceutical Sciences at the University of São Paulo (FCFAr-Unesp), Araraquara campus. The results of the perform, supported by FAPESP and published in the journal ACS Omega, suggest a possible new path for shorter, less toxic, and more effective therapies against resistant bacteria – one of the biggest current challenges in combating the disease.
Tuberculosis, while centuries old and curable, remains the leading infectious cause of death worldwide. Current treatment protocols require at least six months of daily medication with at least four antibiotics, and can extend to two years in cases of drug resistance, hindering adherence and contributing to treatment failure.
“The disease is curable, but the treatment is long and arduous. Patients grab several antibiotics every day, which can cause side effects and affect the kidneys and liver,” explains Fernando Rogério Pavan, advisor to the study and coordinator of the Drug Research area against Tuberculosis at the Rede-TB.
The World Health Organization (WHO) estimates that without treatment, the mortality rate from tuberculosis can reach 50%. However, when the regimen is followed correctly, about 85% of patients recover. But the Brazilian epidemiological scenario reinforces the importance of searching for new drugs against the disease: the Ministry of Health recorded 84,308 new cases of tuberculosis in 2024 and 6,025 deaths in 2023, the highest number in more than two decades. This data is the most recent and was released in 2025.
Even with free treatment available through the Unified Health System (SUS), the researcher explains that correct adherence is particularly challenging in more vulnerable populations, such as people experiencing homelessness or with alcohol dependence. “You’ll see patients who interrupt the apply of antibiotics midway through the cycle, which leads to bacterial resistance. Many patients end up with no therapeutic options, as the bacteria resist everything available. And this person can transmit this resistant strain to another, creating an even more dangerous cycle,” Pavan emphasizes.
The Study’s Genesis
The group led by Pavan has been studying potential actions of molecules against tuberculosis for about 20 years. This time, in the doctoral research of Fernanda Manaia Demarqui, the idea was to investigate ferroin – scientific name [Fe(phen)3]2+], a very old compound (it has existed since the 1950s) traditionally used in chemical syntheses.
The proposal stemmed from drug repositioning – testing known substances for new therapeutic uses. “We didn’t invent a new molecule. We took an old substance, cheap, soluble in water, and tested it for tuberculosis. When we saw antimicrobial activity, we thought: this could become a thesis,” the researcher says.
In laboratory tests, FEP showed strong action against the tuberculosis bacillus, even enhancing the action of rifampicin and pretomanid, two drugs used to treat the disease. The group was able to discover the mechanism of action of the substance.
According to Pavan, microscopy and genomic sequencing showed significant damage to the bacterial cell wall, suggesting an action similar to that of penicillins. “We discovered that it acts by inhibiting the synthesis of the cell wall. Microscopy shows the morphology of the bacteria completely altered and mutations in its genome correspond to proteins of the cell wall,” Pavan explains.
Because it is an “unstable” substance that could be degraded in the stomach, the researchers encapsulated the compound in lipid nanoparticles (NLS@FEP), which act as a “controlled release packaging.” This improved its stability and time of action in the body. “This capsule protects the substance and allows for gradual release, keeping the compound active for longer. It is a simple formulation, made with cholesterol and phosphatidylcholine, of low cost and easy production,” says the researcher.
The next step was to test the compound in animals. They were divided into groups of seven mice infected with Mycobacterium tuberculosis – half were treated conventionally and half received the compound. After 30 days, the group observed complete elimination of pulmonary infection with both free FEP and the encapsulated form. The performance surpassed that of isoniazid, one of the standard antibiotics in SUS.
“The result surprised us very positively because we were hoping to see some reduction in the bacterial load. But the tests showed that the compound eliminated everything. We found no bacilli in the lung. In the group treated with conventional antibiotics, there was a reduction in the bacterial load, as expected,” he reports.
Despite the encouraging results, it is not yet possible to talk about clinical application. Toxicity studies, pharmacokinetics, and more robust trials will be necessary, including models of resistant tuberculosis and cases of chronic infection. Pavan points out, however, that the fact that the compound is not patented could facilitate future advancement towards industrial development. “This could be of particular interest to the public sector. If it works, it will be possible to transform the substance into a medicine without great costs.”
If new studies confirm efficacy and safety in humans, Pavan hopes the compound will pave the way for shorter treatments, with fewer side effects and greater adherence, reducing the risk of resistance and the impact of the disease in the country. “The main thing we already realize: it works. Now we necessitate to adjust the dose, duration of use, repeat tests and move forward. But seeing total elimination in an animal model gives us hope,” he concludes.
The article [Fe(phen)3]2+] and [Fe(phen)3]2+]-loaded nanostructured lipid system: in silico, in vitro, and in vivo efficacy against Mycobacterium tuberculosis can be read at: pubs.acs.org/doi/10.1021/acsomega.5c08350.
