Facile Homobifunctional Imidoester Modification of Advanced Nanomaterials for Enhanced Antibiotic Synergistic Effect

Resistance to antibiotics because of misuse and overuse is one of the greatest public health challenges worldwide. Despite the introduction of advanced nanotechnology in the production of antibiotics, the choice of appropriate medicines is limited due to side effects such as blood coagulation, toxicity, low efficacy, and low biocompatibility; therefore, novel nanomaterial composites are required to counter these repercussions. We first introduce a facile method for synthesizing a homobifunctional imidoester-coated nanospindle (HINS) zinc oxide composite for enhancement of antibiotic efficacy and reduction of toxicity and blood coagulation. The antibiotic efficacy of the composites is twice that of commercialized zinc nanoparticles; in addition, they have good biocompatibility, have increased surface charge and solubility owing to the covalent acylation groups of HI, and produce a large number of Zn⁺ ions and defensive reactive oxygen species (ROS) that effectively kill bacteria and fungi. The synergistic effect of a combination therapy with the HINS composite and itraconazole shows more than 90% destruction of fungi in treatments with low dosage with no cytotoxicity or coagulation evident in intravenous administration in in vitro and in vivo experiments. Thus, HINS composites are useful in reducing the effect of misuse and overuse of antibiotics in the medical field.