Temperature/pH-Sensitive Nanoantibiotics and Their Sequential Assembly for Optimal Collaborations between Antibacterial and Immunoregulation.

Treatment of bacterial infections due to the fast emergence of drug-resistant bacteria is a significant challenge faced in modern medicine. Here the authors report a drug-induced self-assembly nanoantibiotic for treating bacterial infection, with temperature/pH-sensitivity, synergistic antibacterial effect of silver and antibiotics, and immunoregulatory effect. In this nanoantibiotic, smart polymer p(N-isopropylacrylamide-b-acrylic acid) triblock polymer (PNA) utilized to encapsulate the drugs provides convenience in preparing this structure simply through drug-induced self-assembly and controllable release profile by changing the sequence of addition of different drugs. The polymer also allows the nanoantibiotic to be responsive to multiple external stimuli such as pH, temperature, and ionic strength. The silver and antibiotics codelivered in this nanoantibiotic can exert a synergistic antibacterial effect due to the different antibacterial mechanisms. More importantly, macrophages can be activated into an M2 phenotype to promote tissue repair by this nanoantibiotic for the negative surface charge and the antibiotics contained. The self-assembly nanoantibiotic exhibited great promise to be applied in the treatment of bacterial infection and provide favorable utility for inflammation treatment, tissue engineering, and targeted therapy.