S-thanatin (Ts) was a short
antimicrobial peptide with selective antibacterial activity. In this study, we aimed to design a
drug carrier with specific bacterial targeting potential. The positively charged Ts was modified onto the
liposome surface by linking Ts to the constituent
lipids via a PEG linker. The benefits of this design were evaluated by preparing a series of
liposomes and comparing their
biological effects in vitro and in vivo. The particle size and Zeta potential of the constructed
liposomes were measured with a Zetasizer Nano ZS system and a confocal
laser scanning microscope. The in vitro
drug delivery potential was evaluated by measuring the cellular uptake of encapsulated
levofloxacin using HPLC. Ts-linked
liposome or its conjugates with
quantum dots favored bacterial cells, and increased the bacterial uptake of
levofloxacin. In antimicrobial assays, the Ts and
levofloxacin combination showed a synergistic effect, and Ts-LPs-LEV exhibited excellent activity against the quality control
stain Klebsiella pneumoniae ATCC 700603 and restored the susceptibility of multidrug-resistant K. pneumoniae clinical isolates to
levofloxacin in vitro. Furthermore, Ts-LPs-LEV markedly reduced the lethality rate of the
septic shock and resulted in rapid bacterial clearance in mouse models receiving clinical multidrug resistant (MDR) isolates. These results suggest that the Ts-functionalized
liposome may be a promising
antibiotic delivery system for clinical infectious disorders caused by MDR bacteria, in particular the
sepsis related diseases.