Objective:To prepare killer peptide-loaded PLGA nanoparticles which have better effect in treating systemic crypotococcosis.Methods: We adopted a modified double-emulsion method to prepare the killer peptide-loaded PLGA nanoparticles,and the nanoparticles were characterized by using TEM,SEM,Dynamic Laser Scattering,drug loading analysis,ecapsulation efficacy assessment and in vitro release test.We also evaluated the antifungal activities of killer peptide and killer peptide-loaded PLGA nanoparticles against Cryptococcus neoformans ATCC32609 by plate count method.In the in vivo study,the anticryptococcal efficacies of killer peptide and killer peptide-loaded PLGA nanoparticles were compared by observing the survival and colony-forming in vital organs in a systemic murine cryptococcosis model.Results: We successfully synthesized killer peptide-loaded PLGA nanoparticles.In vitro anticryptococcal test showed that the killer peptide and killer peptide-loaded PLGA nanoparticles had significantly stronger anticryptococcal effect compared with the normal saline group (P<0.05),and there was no significant difference in the efficacies between free killer peptide and killer peptide-loaded PLGA nanoparticles (P>0.05).In vivo test demonstrated that mice treated with killer peptide-loaded PLGA nanoparticles (3 mg/kg or 5 mg/kg) had longer survival period and less fungal burden in vital organs than mice treated with free killer peptide (P<0.05); there was no significant difference in fungal burden and survival period between empty PLGA nanoparticle treated group and normal saline group (P>0.05).Conclusion: The killer peptide-loaded PLGA nanoparticles are more effective in treating systemic murine cryptococcosis.