Targeted Delivery Of Artemisinin By Heparin-modified Inorganic Nanomaterials For Malaria Treatment

Malaria is one of the three major infectious diseases in the world.It is widely prevalent in sub-Saharan Africa,and it is a global public health problem.A variety of mammals are known to be infected with malaria,including monkeys,mice,guinea pigs and rabbits.Artemisinin is a first-line antimalarial drug used in the clinical treatment of malaria.However,the prevalence of artemisinin-resistant parasites in Southeast Asia poses a serious challenge to malaria control.A number of strategies have been used to overcome drug resistance of malaria parasites,including the development of new vaccines and the development of efficient drug delivery systems.Screening of nanomedicine for targeted therapy of malaria is becoming a research hotspot.Plasmodium falciparum catabolized hemoglobin in red blood cells and produces hemozoin.Paramagnetic hemozoin is ideal targets for magnetic nanomaterials.Heparin is an important receptor for the invasion of merozoites into red blood cells.Nanomaterials using heparin as a targeting molecule have great prospects in the targeted treatment of malaria.In this study,we obtained hollow mesoporous ferrite nanoparticles(HMFNs)with the size of 196 nm.Make the use of magnetic targeting,HMFNs can target Plasmodium falciparum containing hemozoin.After coating with heparin(HMFNs@HEP),HMFNs can target the merozoites of Plasmodium falciparum and the parasitemia was significantly decreased because of the blocking of HMFNs@HEP to merozoites.HMFNs@HEP@ART was obtained by loading artemisinin.Compared with free artemisinin,HMFNs@HEP@ART exhibited better anti-malarial effect in vitro.These results provide new ideas for targeted treatment of Plasmodium falciparum.In addition,graphene quantum dots(GQDs)have great application potential in biomedicine due to their luminescence and high drug loading effect.Herein,GQDs with 3.35 nm were synthesized in the use of strong acid oxidation reaction.Our results show that graphene quantum dots can enter infected red blood cells and inhibit the proliferation of Plasmodium falciparum.Transcriptome analysis showed that graphene quantum dots could induce apoptosis of Plasmodium falciparum and disrupt ligand-receptor interaction between Plasmodium falciparum and red blood cells.All of those inhibit the growth of Plasmodium falciparum.After chemically modified with heparin(GQDs@HEP),graphene quantum dots can target Plasmodium falciparum merozoites.GQDs@HEP@ART was obtained by loading artemisinin.Compared with free artemisinin,GQDs@HEP@ART exhibited stronger anti-malarial effect in vitro.In therapeutic trials of murine malaria,artemisinin had better therapeutic effects than nanomaterials.This suggests that we need to optimize the synthesized nanomaterials to cope with the complex environment in vivo for the application in the treatment of malaria.In this study,we constructed targeted nanomaterials with potential application in the treatment of malaria,which provides more ideas for the efficient treatment of Plasmodium falciparum.