Neomycin loaded by tetrahedral framework nucleic acids enhances antimicrobial sensitivity against bacteria

Burn wound infections pose significant challenges to the management of burn injuries. Antibiotic therapy now is playing a crucial part in preventing and treating post-burn infections. Neomycin sulfate (NeoS; one of the most commonly used antibiotics for treating multiple bacterial infections) faces limitations such as low bioavailability and severe side effects. Therefore, there is an urgent need for strategies to improve the therapeutic efficacy of NeoS. We proposed a strategy combining NeoS with nanomaterials, specifically using tetrahedral framework nucleic acids (tFNAs) as a carrier to load NeoS and fabricate tFNAs-loading NeoS (tFNAs-NeoS). This design made antibiotics more sensitive to <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>, enabling reduced antibiotic doses. Moreover, tFNA-NeoS exhibited improved stability, biocompatibility, and tissue utilization compared with free NeoS. Leveraging these advantages, tFNA-NeoS was tested <i>in vivo</i> using rats, and results further demonstrated its role in anti-inflammation activity, activating angiogenesis, and promoting wound healing. Thus, this strategy of using tFNAs to deliver antibiotics holds promise for enhancing antibiotic sensitivity and minimizing adverse effects in broader antibacterial scenarios.