Allicin-based biomimetic nanoparticles of the erythrocyte membrane for the delivery of lumefantrine to enhance its antimalarial effect

Owing to the emergence of drug resistance and the lack of effective vaccines, malaria continues to seriously harm the physical and mental health of multitude of individuals, warranting the need of exploring new antimalarial strategies. In this study, we developed allicin-based biomimetic nanoparticles of erythrocyte membrane (PECm-Allicin@LM) by ultrasound for the delivery of lumefantrine (LM), a hydrophobic anti-malarial drug. PECm-Allicin@LM showed regular spheres with a mean diameter of 120 nm, and retained almost the major proteins on the erythrocyte membrane. PECm-Allicin@LM was stable and sustained release LM. Flow cytometry analysis showed that PECm-Allicin@LM could deliver LM to Plasmodium -infected erythrocytes to kill the parasite. The nanoparticles, disguised as erythrocytes, could trap merozoites and competitively inhibited them from repeatedly infecting normal erythrocytes. Allicin in nanoparticles not only dissolved LM but could also disrupted the mitochondrial function of malaria parasites, working together to combat malaria and improve the immune dysfunction caused by malaria. Giemsa staining was performed to determine the infection rate in Pb ANKA-infected mice. In Plasmodium berghei ANKA strain-infected ICR mice, PECm-Allicin@LM significantly reduced the infection rates, prolonged the survival time, and attenuated the Plasmodium- induced weight loss, anemia, and organ injury. Overall, these nanoparticles combine the advantages offered by the erythrocyte membrane, allicin, and LM to effectively combat malaria, representing a new antimalarial strategy targeting multiple pathways. Allicin-based biomimetic nanoparticles of erythrocyte membrane (PECm-Allicin@LM) was developed for the delivery of lumefantrine (LM). PECm-Allicin@LM showed excellent performance, suitable particle size, and good stability. Allicin present in the nanoparticles could not only dissolve LM but also synergistically fought against malaria and improved the malaria infection-induced disruption in immune function, thereby executing the proverbial killing of two birds with one stone. • An allicin-based biomimetic nanoparticles of erythrocyte membrane (PECm-Allicin@LM) for the delivery of lumefantrine (LM). • To target deliver LM to Plasmodium -infected erythrocytes to kill the parasite. • To trap merozoites and competitively inhibited them from repeatedly infecting normal erythrocytes. • Allicin not only synergistically fights against malaria, but also improves the immune function disruption induced by malaria infection.