Recent decrease in theefficacy of the who recommended artemisinin based combination therapies (acts) have been major setback to combat malaria burden.to overcome these setbacks, wedemonstrate both in vitro and preclinical evidence that nontoxic biocompatible iron oxide nanoparticle fortification of artesunate improves the efficacy by 8-10fold against the malaria parasites. sustainedrelease of fe2+ in a ph-dependent manner within the parasite food vacuole enables persistent activation of artesunate and generation of radical species via endoperoxide cleavage. in line with this, combination treated parasites also result in heightened dna damage and irreversible protein damage in comparison to artesunate alone. finally, this study provides a strategic approach for the first time to mediate controlled drug activation, improving artesunate’s activity against artemisinin-resistant and sensitive parasites making artesunate more efficacious for combination therapy.
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