Erythrocyte membrane with CLIPPKF as biomimetic nanodecoy traps merozoites and attaches to infected red blood cells to prevent Plasmodium infection

Background Malaria remains a serious threat to global public health. With poor efficacies of vaccines and the emergence of drug resistance, novel strategies to control malaria are urgently needed. Results We developed erythrocyte membrane-camouflaged nanoparticles loaded with artemether based on the growth characteristics of Plasmodium . The nanoparticles could capture the merozoites to inhibit them from repeatedly infecting normal erythrocytes, owing to the interactions between merozoites and heparin-like molecules on the erythrocyte membrane. Modification with a phosphatidylserine-targeting peptide (CLIPPKF) improved the drug accumulation in infected red blood cells (iRBCs) from the externalized phosphatidylserine induced by Plasmodium infection. In Plasmodium berghei ANKA strain ( pb ANKA)-infected C57BL/6 mice, the nanoparticles significantly attenuated Plasmodium -induced inflammation, apoptosis, and anemia. We observed reduced weight variation and prolonged survival time in pb ANKA-challenged mice, and the nanoparticles showed good biocompatibility and negligible cytotoxicity. Conclusion Erythrocyte membrane-camouflaged nanoparticles loaded with artemether were shown to provide safe and effective protection against Plasmodium infection. Graphical Abstract