Intracellular bacteria can multiply inside host cells and manipulate their biology,and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation.Fighting...Intracellular bacteria can multiply inside host cells and manipulate their biology,and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation.Fighting against these stealthy bacteria has been a longstanding challenge.Here,a system of stimuli-responsive lactoferrin(Lf)nanoparticles is prepared using protein self-assembly technology to deliver broad-spectrum antibiotic rifampicin(Rif)(Rif@Lf NPs)for enhanced infection therapy through targeted elimination of intracellular bacteria.Compared to Rif@BSA NPs,the Rif@Lf NPs can specifically target macrophages infected by bacteria,thus increasing the accumulation of Rif within macrophages.Subsequently,Rif@Lf NPs with positive surface charge further displayed targeted adherence to the bacteria within macrophages and released Rif rapidly in a redoxresponsive manner.Combined with the antibacterial activities of Lf and Rif,the Rif@Lf NPs showed broad-spectrum antibiotic abilities to intracellular bacteria and biofilms.As a result,the Rif@Lf NPs with high safety exhibited excellent therapeutic efficacy in the disease models of subcutaneous infection,sepsis,and bacterial keratitis.Taken together,the antibiotic-loaded Lf nanoparticles present a promising platform to combat pathogen infections through targeted elimination of intracellular bacteria.展开更多
基金support from the National Natural Science Foundation of China(Nos.22275081,82372117)Guangzhou Science and Technology Bureau(202206010068)China Postdoctoral Science Foundation(2022M711532 and 2022T150302).
文摘Intracellular bacteria can multiply inside host cells and manipulate their biology,and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation.Fighting against these stealthy bacteria has been a longstanding challenge.Here,a system of stimuli-responsive lactoferrin(Lf)nanoparticles is prepared using protein self-assembly technology to deliver broad-spectrum antibiotic rifampicin(Rif)(Rif@Lf NPs)for enhanced infection therapy through targeted elimination of intracellular bacteria.Compared to Rif@BSA NPs,the Rif@Lf NPs can specifically target macrophages infected by bacteria,thus increasing the accumulation of Rif within macrophages.Subsequently,Rif@Lf NPs with positive surface charge further displayed targeted adherence to the bacteria within macrophages and released Rif rapidly in a redoxresponsive manner.Combined with the antibacterial activities of Lf and Rif,the Rif@Lf NPs showed broad-spectrum antibiotic abilities to intracellular bacteria and biofilms.As a result,the Rif@Lf NPs with high safety exhibited excellent therapeutic efficacy in the disease models of subcutaneous infection,sepsis,and bacterial keratitis.Taken together,the antibiotic-loaded Lf nanoparticles present a promising platform to combat pathogen infections through targeted elimination of intracellular bacteria.
