Old dogs may not learn new tricks, but old medicines can, according to a China-based research team. The collaboration found that metformin, a small molecule drug used to treat type 2 diabetes for more than 50 years, can improve the efficiency and effectiveness of antibacterial treatments for rapid wound healing in mice.
They published their results on May 19 in Nano Research. (doi 10.1007/s12274-022-4457-5)
Antibiotic abuse has led to serious bacterial resistance, with about 1.27 million deaths in 2019 from multidrug-resistant bacterial infections. Bacterial resistance poses a fatal threat to human health. Non-antibiotic antibacterial technologies and antibacterial nanomaterials 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, dynamic chemotherapy has attracted great interest since it was developed in 2016 as a potential companion to cancer therapies, bacterial inhibition, and treatments for infectious disease. The treatment uses nanomaterials containing transition metals that react with hydrogen peroxide to produce hydroxyl radicals, which weaken and kill diseased or infected cells, making them more susceptible to direct treatment.
“The reaction generates toxic hydroxyl radicals that destroy the cell surface structure and cause the cell to leak its internal components,” Lee told me. “Nanoagents only stimulate the generation of hydroxyl radicals at the site of a tumor or inflamed tissue, so treatment is very specific to reduce off-target toxicity. Bacterial infections also tend to be accompanied by microenvironmental changes favorable to chemotherapy.”
Researchers set out to improve the antibacterial power of the nano-agent, while reducing toxicity to healthy cells -; A risk that is difficult to control due to the invasive nature of the infection.
“Positively charged molecular fragments, such as quaternary ammonium salts and chitosan, have intrinsic antibacterial effects through adsorption on the bacterial cell wall, producing a compartment-resisting effect, and finally causing bacterial death,” Lee said. “Metformin is a positively charged small molecule drug with anticancer, immunomodulatory and antibacterial effects. We speculated that combining metformin with a nano-agent for dynamic chemotherapy would improve the antibacterial effect.”
The researchers stirred metformin with copper chloride to form nanosheets whose surface was covered with metformin particles -; Enhance the positive charge of the nano and strengthen the antibacterial effects, according to Li.
In vitro tests revealed a biocompatible nanoplatform with better metformin-free nano-factor dispersion, and higher antibacterial activity.
“Compared to previous reports that used metformin as an antibacterial agent alone, excellent antimicrobial effects were achieved in our experiments using lower concentrations of nanoparticles with a very short time of action,” Lee said, noting that they are also studying the effects of metformin in others. Biomedical applications to develop more treatments.
To further test the metformin-coated nanosheets, the researchers created a model of staph infection in the skin of mice. The mice were divided into five groups, each group receiving a different treatment. The group that received both metformin nanosheets and supplemental hydrogen peroxide to increase hydroxyl radical production had the fastest wound healing rate, with complete closure by day 12 of treatment.
“This work not only develops an effective chemotherapeutic nano-agent as an antibacterial agent for treating skin wound infections, but also provides insights into discovering new uses for old drugs,” Lee said.
Li also belongs to the Nano-energy Research Center, College of Physical Science and Technology, Guangxi University, and CAS University’s College of Nano Science and Technology. Other contributors include Xueyu Wang and Teng Xu and co-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, Distinguished Medical Center of the People’s Liberation Army Strategic Support Force. Xueyu Wang and Xu also belong to the Beijing Institute of Nanoenergy and Nanosystems, CAS, and the Medical Center of Excellence for the People’s Liberation Army Strategic Support Force. Shaobo Wang, Zhao, Zhang and Huang are also affiliated with the Nano-energy Research Center, College of Physical Sciences and Technology, Guangxi University. Yao also belongs to CAS University’s School of Nano Science and Technology.
The National Natural Science Foundation of China and the National Youth Talent Support Program supported this work.
Tsinghua University Press
Wang, X., et al. (2022) Metformin coated Cu2(OH)3Cl nanosheets for dynamic chemical wound disinfection. Nano Research. doi.org/10.1007/s12274-022-4457-5.