Tetrahedral Framework Nucleic Acids Loading Ampicillin Improve the Drug Susceptibility against Methicillin-Resistant Staphylococcus aureus

• Published in: ACS applied materials & interfaces Vol. 12; no. 33; pp. 36957 - 36966
• Main Authors: Sun, Yue, Li, Songhang, Zhang, Yuxin, Li, Qirong, Xie, Xueping, Zhao, Dan, Tian, Taoran, Shi, Sirong, Meng, Lingxian, Lin, Yunfeng
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19.08.2020
• Subjects: Ampicillin - chemistry; Ampicillin - pharmacology; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biological and Medical Applications of Materials and Interfaces; Cell Membrane Permeability; Drug Carriers - chemistry; Drug Liberation; Drug Resistance, Microbial; Drug Synergism; Gene Expression Regulation, Bacterial; Human Umbilical Vein Endothelial Cells; Humans; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; Nucleic Acids - chemistry; Pharmaceutical Preparations; drug delivery system; penicillin binding protein; antibiotic resistance; tetrahedral framework nucleic acids; methicillin-resistant Staphylococcus aureus (MRSA)
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.0c11249

The overuse of antibiotics has led to the emergence of multidrug-resistant pathogens. There is an urgent need to develop alternative therapeutic strategies to reduce mortality and morbidity related to drug-resistant bacterial infections. Self-synthesized tetrahedral framework nucleic acids (tFNAs) are used as the drug loading platform to deliver ampicillin to combat methicillin-resistant Staphylococcus aureus (MRSA) infection. The results of average dimension, zeta potential, transmission electron microscopy, and ultraviolet spectrophotometry showed that tFNAs-ampicillin combined with a sufficient encapsulation rate and good stability. tFNAs-ampicillin had a better affinity to MRSA than free ampicillin because it had a better uptake by MRSA cells. Additionally, tFNAs-ampicillin had a better antibacterial effect and lower levels of resistance development than free ampicillin. The downregulation of genes related to bacterial cell wall synthesis (murA and murZ) and upregulation of a gene related to antibiotic sensibility (PBP2) were responsible for the enhanced killing effect of tFNAs-ampicillin against MRSA.