A study led by Xavier Fernández Busquets, director of the joint ISGlobal-IBEC Nanomalaria unit, describes an innovative approach to selectively eliminate red blood cells infected by Plasmodium falciparum, avoid their aggregation, and inhibit parasite growth.
The strategy, based on the use of nanovesicles coated with antibodies that target a parasite protein, and loaded with an antimalarial drug, represents a promising alternative in the treatment of severe malaria.
The combination therapy described in the study has the advantage of delaying the development of resistance in the parasite.
Red blood cells (erythrocytes) infected by the malaria parasite express a parasite protein at the cell surface (the PfEMP1 protein) that allows them to adhere to the cells lining the blood vessels and evade their clearance. In addition, PfEMP1 is one of the molecules responsible for the aggregation (or rosetting) of infected erythrocytes, which leads to clot formation and contributes to the fatal outcome of severe malaria.
In this study, the authors sought to inhibit erythrocyte resetting in vitro (i.e. in the laboratory) through the use of nanovesicles (liposomes) coated with anti-PfEMP1 antibodies and loaded with an antimalarial drug (lumefantrine). They found that the immunoliposomes specifically targeted infected erythrocytes and physically disrupted rosette formation. In addition, they delivered the drug to the infected cells, thereby inhibiting parasite growth.
This study provides a proof-of-concept that approaches that combine two different mechanisms of action against the parasite represent a promising therapy for severe malaria. “The chance that a parasite becomes resistant to two drugs with unrelated modes of action simultaneously is very low,” explains Fernández-Busquets. “Thus, combination therapies delay the evolution of resistance in the parasite and can therefore contribute to eradicating malaria.”
Moles E, Moll K, Ch’ng JH, Parini P, Wahlgren M, Fernàndez-Busquets X. Development of drug-loaded immunoliposomes for the selective targeting and elimination of rosetting Plasmodium falciparum-infected red blood cells. J Control Release. 2016 Sep 13; 241:57-67.