Biologically active polymer core/shell nanoparticles (i.e. micelles) self-assembled from TAT-poly(ethylene glycol) (PEG)-b-cholesterol (TAT-PEG-b-Chol) were fabricated and used as carrier for targeted blood-brain barrier delivery of antibiotics. Ciprofloxacin as a model antibiotic was efficiently loaded into the nanoparticles by a membrane dialysis method. The actual loading level of ciprofloxacin was dependent on initial loading of ciprofloxacin and fabrication temperature. The blank and ciprofloxacin-loaded nanoparticles were characterized using dynamic light scattering and SEM. The nanoparticles were spherical in nature, having an average size lower than 200 nm. The uptake of nanoparticles with TAT by human brain endothelial cells was greater than that of the nanoparticles without TAT. Most importantly, the nanoparticles with TAT were able to cross the blood-brain barrier (BBB), and located around the cell nucleus of neurons. These nanoparticles may provide a promising carrier to deliver antibiotics across the BBB for the treatment of brain infection.