Infection-responsive polysaccharide-based drug-loaded nano-assembly for dual-modal treatment against drug-resistant bacterial lung infection

The escalating issue of lung infections induced by multi-drug resistant (MDR) bacteria is threatening human health. Thus, the development of efficient drug delivery systems is essential to eliminate MDR bacterial lung infections effectively. Herein, we designed inhalable drug-loaded nano-assemblies by the electrostatic interaction between negatively charged sodium alginate and a positively charged antibacterial polymer, quaternized polyethyleneimine (QPEI-C6), as well as a kind of typical antibiotic for therapy of lung infection, azithromycin (AZT). By adjusting the feed ratios, we optimized the size of the nano-assembly to approximately 200 nm (STQ12), which was beneficial for penetration through the mucus layer and biofilm. In the slightly acidic environment of the infected site, the nano-assembly could dissemble responsively and release AZT and QPEI-C6. Because of the combined bactericidal effect, STQ12 exhibited high bactericidal efficiency against MDR bacteria. In animal experiments, STQ12 showed notable efficacy against MDR bacterial lung infection. Gene transcriptomic results showed that the main effects of STQ12 against bacteria were through influencing the bacterial cell components and metabolic processes, and affecting their growth and reproduction. This work provides a promising strategy to treat MDR bacterium-induced lower respiratory tract infections. A kind of infection-responsive drug-loaded nano-assembly, STQ12, was developed by the electrostatic interaction between negatively charged polysaccharide and positively charged quaternized ammonium salt polymer. STQ12 could penetrate the mucus layer rapidly and reach the acidic microenvironment at the infected site, releasing the loaded drug and QPEI-C6 to realize combined anti-infection therapy against multi-drug resistant bacteria.image