Nanosilver-Decorated Biodegradable Mesoporous Organosilica Nanoparticles for GSH-Responsive Gentamicin Release and Synergistic Treatment of Antibiotic-Resistant Bacteria

Haijun Li,1,* Dongbei Li,2,* Fangman Chen,3 Chao Yang,3 Xiaogai Li,1 Yuan Zhang,1 Chunlan Hua,1 Xiaoxu Ma,1 Xin Zhao,1 Dan Shao,3 Yingshuai Wang,4 Liang Ming1 1Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 2Department of Hematology, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450000, People’s Republic of China; 3Institutes for Life Sciences, School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 510630, People’s Republic of China; 4School of Life Science and Technology, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingshuai WangSchool of Life Science and Technology, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of ChinaEmail yingshuaiwang1987@163.comLiang MingDepartment of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaEmail mingliang3072@163.comPurpose: Antibiotic-resistant bacteria are pathogens that have emerged as a serious public health risk. Thus, there is an urgent need to develop a new generation of anti-bacterial materials to kill antibiotic-resistant bacteria.Methods: Nanosilver-decorated mesoporous organosilica nanoparticles (Ag-MONs) were fabricated for co-delivery of gentamicin (GEN) and nanosilver. After investigating the glutathione (GSH)-responsive matrix degradation and controlled release of both GEN and silver ions, the anti-bacterial activities of Ag-MONs@GEN were systematically determined against several antibiotic-susceptible and antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Furthermore, the cytotoxic profiles of Ag-MONs@GEN were evaluated.Results: The GEN-loaded nanoplatform (Ag-MONs@GEN) showed glutathione-responsive matrix degradation, resulting in the simultaneous controlled release of GEN and silver ions. Ag-MONs@GEN exhibited excellent anti-bacterial activities than Ag-MONs and GEN alone via inducing ROS generation, especially enhancing synergetic effects against four antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Moreover, the IC50 values of Ag-MONs@GEN in L929 and HUVECs cells were 313.6 ± 15.9 and 295.7 ± 12.3 μg/mL, respectively, which were much higher than their corresponding minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values.Conclusion: Our study advanced the development of Ag-MONs@GEN for the synergistic and safe treatment of antibiotic-resistant bacteria.Keywords: mesoporous organosilica nanoparticles, nanosilver, gentamicin, GSH-responsive release, antibiotics-resistant bacteri