Malaria is one of the deadliest infectious
diseases threatening
half of the world population. With the deterioration of the parasiticidal
effect of the current antimalarials, novel approaches such as screening
of more specific inhibitors and targeted delivery of drugs have been
under intensive research. Herein, we prepare hollow mesoporous ferrite
nanoparticles (HMFNs) of 200 nm with ferromagnetic properties using
a one-pot hydrothermal reaction. A magnetically targeted drug-delivery
system coloaded with artemisinin in the inner magnetite shell and
heparin on the outer mesoporous shell (HMFN@ART@HEP) is developed.
Specific targeting of the magnetic nanoparticles to the parasite-infected
erythrocytes is achieved by the attraction between the HMFNs and hemozoin
(paramagnetic), a vital metabolite of plasmodium in the erythrocytic
stage. With the hemozoin production reaching the maximum during the
schizont period of the parasite, HMFN@ART@HEPs are adsorbed to the
infected red blood cells (iRBCs), which not only interferes with the
release of merozoites but also significantly enhances the inhibitory
efficacy due to the increased local concentration of artemisinin.
Subsequently, the heparin coated on the surface of the nanoparticles
can efficiently interfere with the invasion of freshly released merozoites
to new RBCs through the specific interaction between the parasite-derived
ligands and heparin, which further increases the inhibitory effect
on malaria. As a cluster of heparin, heparin-coated nanoparticles
provide stronger blocking capability than free heparin, resulting
from multivalent interactions with surface receptors on merozoite.
Thus, we have developed a HMFN-based delivery system with considerable
antimalarial efficacy, which is a promising platform for treatment
against malaria.