title: Nanomimics of host cell membranes block invasion and expose invasive malaria parasites.
abstract: The fight against most infectious diseases, including malaria, is often hampered by the emergence of drug resistance and lack or limited efficacies of vaccines. Therefore, new drugs, vaccines, or other strategies to control these diseases are needed. Here, we present an innovative nanotechnological strategy in which the nanostructure itself represents the active substance with no necessity to release compounds to attain therapeutic effect and which might act in a drug- and vaccine-like dual function. Invasion of Plasmodium falciparum parasites into red blood cells was selected as a biological model for the initial validation of this approach. Stable nanomimics-polymersomes presenting receptors required for parasite attachment to host cells-were designed to efficiently interrupt the life cycle of the parasite by inhibiting invasion. A simple way to build nanomimics without postformation modifications was established. First, a block copolymer of the receptor with a hydrophobic polymer was synthesized and then mixed with a polymersome-forming block copolymer. The resulting nanomimics bound parasite-derived ligands involved in the initial attachment to host cells and they efficiently blocked reinvasion of malaria parasites after their egress from host cells in vitro. They exhibited efficacies of more than 2 orders of magnitude higher than the soluble form of the receptor, which can be explained by multivalent interactions of several receptors on one nanomimic with multiple ligands on the infective parasite. In the future, our strategy might offer interesting treatment options for severe malaria or a way to modulate the immune response.
authors.affiliation: Department of Chemistry, University of Basel , Klingelbergstrasse 80, CH-4056 Basel, Switzerland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Najer
authors.forename: Dalin
authors.initials: D
authors.lastname: Wu
authors.forename: Andrej
authors.initials: A
authors.lastname: Bieri
authors.forename: Françoise
authors.initials: F
authors.lastname: Brand
authors.forename: Cornelia G
authors.initials: CG
authors.lastname: Palivan
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Beck
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meier
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry* / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000469:parasitology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008288:Malaria / Q000469:parasitology*; D049329:Nanostructures; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000502:physiology*
keywords: Plasmodium; block copolymer; infectious disease; nanomedicine; polymersome; self-assembly; vesicle