Multifunctional Framework Nucleic Acid Vehicle for Antibiotic Sensitization and Treatment of Methicillin‐Resistant Staphylococcus aureus

作者：Yicheng Zhao, Jingyi Si, Shisong Jing, Bingmei Wang, Yueshan Xu, Jiyu Guan, Quan Liu, Jianlei Shen, Min Lv, Li Wang, Changfeng Zhu · 发表于：Aggregate · 年份：2025 · DOI：10.1002/agt2.70059 · 被引用次数：7 · 研究领域：Advanced biosensing and bioanalysis techniques、Antimicrobial Resistance in Staphylococcus、Biosensors and Analytical Detection

ABSTRACT The increasing prevalence of methicillin‐resistant Staphylococcus aureus (MRSA) due to antibiotic misuse necessitates novel therapeutic strategies to counter multidrug‐resistant infections. Here, we introduce a self‐assembling, aggregation‐enhanced tetrahedral DNA nanostructure (tFNA) platform that achieves targeted drug delivery through controlled aggregation and sustained release, effectively restoring MRSA susceptibility to β‐lactam antibiotics. These tetrahedral frameworks, termed tFNAs‐ASOs‐ceftriaxone sodium (TACs), serve as a dual‐functional system that co‐encapsulates antisense oligonucleotides (ASOs) targeting the mecA gene and the β‐lactam antibiotic ceftriaxone sodium (Cef). Aggregation of TACs plays a pivotal role in maximizing drug retention and stability, prolonging the localized release of both ASOs and antibiotics while maintaining high bioavailability at the infection site. Characterization studies, including size distribution, zeta potential, and fluorescence quenching assays, confirm their robust aggregation stability and encapsulation efficiency, ensuring controlled drug kinetics and prolonged therapeutic effects. Upon interaction with bacterial cells, the locally concentrated TACs facilitate efficient ASO‐mediated mecA silencing, thereby disrupting PBP2a expression and re‐sensitizing MRSA to β‐lactams. Simultaneously, the aggregated ceftriaxone sodium reservoir ensures sustained inhibition of bacterial cell wall synthesis, leading to effective ba...