Old dogs may not learn new tricks, but old drugs may, according to a research team based in China. The collaboration found that metformin, a small molecule drug that has been used to treat type II diabetes for more than 50 years, can improve the efficiency and effectiveness of antibacterial treatments for the rapid cure of wounds in mice.
They published their findings on May 19 in Nano Research. (DOI 10.1007 / s12274-022-4457-5)
Antibiotic abuse has led to severe bacterial resistance, with about 1.27 million deaths in 2019 due to bacterial infections resistant to multiple drugs. Bacterial resistance poses a deadly threat to human health. Non-antibacterial antibacterial technologies and antibacterial nanoagents with specific catalytic activities not only produce toxic substrates to directly kill bacteria -; including antibiotic-resistant bacteria -; but it can also reduce the risk of bacteria developing drug resistance. “
Linlin Li, Professor, Co-author, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences
According to Li, chemodynamic therapy has attracted significant attention since it was developed in 2016 as a potential companion for therapies for cancer, bacterial inactivation, and treatments for infectious diseases. Therapy uses transition metal-containing nanomaterials that react with hydrogen peroxide to produce a hydroxyl radical, which weakens and kills diseased or infected cells, making them more susceptible to direct treatment.
“The reaction generates a toxic hydroxyl radical, which destroys the structure of the cell surface and causes the cell to filter its internal components,” Li said. “Nanoagents only catalyze the generation of hydroxyl radicals at the site of the tumor or inflamed tissues, so therapy is very specific to reduce off-target toxicity. Bacterial infections are also often accompanied by favorable microenvironmental alterations for in chemodynamic therapy “.
The researchers set out to improve the antibacterial power of a nanoagent, while reducing the toxicity to healthy cells -; a risk that can be difficult to control due to the invasive nature of the infection.
“Positively charged parts of molecules, such as quaternary ammonium salts and chitosan, have intrinsic antibacterial effects by adsorption to the bacterial cell wall, producing a compartment resistance effect and ultimately inducing death. bacterial, “Li said. “Metformin is a positively charged small molecule drug with reported anticancer, immunomodulatory, and antibacterial effects. We have speculated that the integration of metformin with a chemodynamic therapy nanoagent will enhance the antibacterial effect.”
The researchers stirred metformin with copper chloride to form nanofoules whose surface was covered by metformin molecules -; improving the positive charge of the nanoagent and enhancing the antibacterial effects, according to Li.
In vitro tests revealed a biocompatible nanoplatform with better dispersion than a nanoagent without metformin and higher antibacterial activity.
“Compared to previous reports of using metformin as the only antibacterial agent, excellent antimicrobial effects were achieved in our experiments using lower concentrations of nanowires with a very short time to action,” said Li, who noted who are also studying the effects of metformin in other biomedical applications to develop further therapies.
To further test nanosheets with metformin, the researchers established a model of staphylococcal infection in the skin of mice. Mice were divided into five groups, each of which received a variation of treatment. The group that received both metformin nanosheets and additional hydrogen peroxide to increase hydroxyl radical production had the fastest wound healing rate, with a complete closure on day 12 of treatment.
“This work not only develops a nanoagent for chemodynamic therapy that is effective as an alternative antibacterial agent for treating skin wound infections, but also provides ideas for discovering new uses for old drugs,” Li said.
He is also affiliated with the Nanoenergy Research Center, Guangxi University School of Physical Science and Technology and CAS School of Nanoscience and Technology. Other contributors include Xueyu Wang, Teng Xu and corresponding author Shu Yan, 306th Clinical College of PLA, The Fifth Clinical College, Anhui Medical University; Shaobo Wang, Shuncheng Yao, Yunchao Zhao, Zeyu Zhang and Tian Huang, Beijing Institute of Nanoenergy and Nanosystems, CAS; Xueyu Wang and Jiao Gao, medical center characteristic of the PLA’s strategic support force. Xueyu Wang and Xu are also affiliated with the Beijing Institute of Nanoenergy and Nanosystems, CAS, and the PLA Strategic Support Force Characteristic Medical Center. Shaobo Wang, Zhao, Zhang and Huang are also affiliated with the Nanoenergy Research Center of Guangxi University School of Physical Science and Technology. Yao is also affiliated with the School of Nanoscience and Technology at CAS University.
The National Foundation for Natural Sciences of China and the National Youth Talent Support Program supported this work.
Source:
Tsinghua University Press
Magazine reference:
Wang, X., et al. (2022) Metformin-coated Cu2 (OH) 3Cl nanowires for disinfection of chemodynamic wounds. Nano Research. doi.org/10.1007/s12274-022-4457-5.