Screening Of Nanomaterials Antimalarial Activity And Further Identification Of Fe²⁺ PP

Background Malaria is a global parasitic infectious disease whose main vector is Anopheles mosquito,which has caused a huge health burden to the world.Of the five malaria parasites that cause human malaria,Plasmodium falciparum is the deadliest.However,antimalarial drug resistance is a recurring problem.P.falciparum has developed resistance to artemisinin.With the rapid development of nanotechnology,metal nanoparticles have been found to have broad prospects in antimalarial treatment.The clinical symptoms are caused by the erythrocyte stage parasites.The infected red blood cells under a severe oxidative stress,then the iron homeostasis disrupting is thought to be an attractive strategy for malaria treatment.Objective This study is based on the identification of P.falciparum phenotype,screening potential antimalarial iron-based nanomaterials,and analyzing the mechanism of nanoparticle(Fe2+PP)killing parasites,which will provide a basis for the development of new antimalarial drugs.Methods Five strains of P.falciparum,including 3D7,SBC,803,Dd2,and K1 were cultured in vitro,and their phenotypic characteristics,such as blood cycle,appearance,and DNA content were analyzed.The SYBR Green I method was used to screen the antimalarial activity and binding efficiency of the four iron-based nanomaterials.Furthermore,through the SYBR Green I method and Pearson's four-day inhibition experiment,the growth inhibition effect of nanoparticles Fe2+PP on different P.falciparum strains in vitro and in vivo was investigated.To explore the mechanism of antimalarial effects of Fe2+PP through the red blood cell hemolysis experiment,cytotoxicity testing and the detection of changes in the intracellular antioxidant index MDA and GSH/GSSG values after treatment with the Fe2+PP.Results By studying the phenotypes of different P.falciparum strains,it was found that the development cycle,appearance and DNA content of different P.falciparum strains in different stages are inconsistent.By screening four kinds of nanomaterials with iron as the core,we found that the Fe2+ PP has the best antimalarial effect.In.vitro sensitivity tests found that Fe2+ PP has a strong killing effect on P.falciparum 3D7,SBC,803,Dd2 and K1,with IC50 of 19.6?mol/1,42.6 pmol/1,35.7 ?mol/1,49.7 ?mol/1,58.7 ?mol/1.In vivo sensitivity test found that Fe2+PP can significantly inhibit the growth of Plasmodium berghei in mice.Flow cytometry results show that Fe2+ PP does not bind to red blood cells infected with P.falciparum.Compared with normal erythrocytes,the GSH/GSSG ratio of the host erythrocytes after Fe2+ PP treatment decreased and the MDA content increased,without causing hemolysis.Conclusion Different strains of Plasmodium have different phenotypes,and related studies should include multiple strains to be comparable.The nanoparticle Fe2+PP has a good antimalarial effect both in vivo and in vitro,the antimalarial mechanism may be due to Fe2+ PP reducing the antioxidant capacity of the cell and increasing the oxidative stress in the cell,which needs further study.