title: Receptor-mediated endocytosis for drug delivery in African trypanosomes: fulfilling Paul Ehrlich's vision of chemotherapy.
abstract: Bloodstream-form cells of Trypanosoma brucei exhibit massively increased endocytic activity relative to the insect midgut stage, enabling rapid recycling of variant surface glycoprotein and antibody clearance from the surface. In addition, recent advances have identified a role for receptor-mediated endocytosis in the uptake of the antitrypanosomal drug, suramin, via invariant surface glycoprotein 75, and in the uptake of trypanosome lytic factor 1 via haptoglobin-haemoglobin receptor. Here, we argue that receptor-mediated endocytosis represents both a validated drug target and a promising route for the delivery of novel therapeutics into trypanosomes.
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. sam.alsford@lshtm.ac.uk
authors.forename: Sam
authors.initials: S
authors.lastname: Alsford
authors.forename: Mark C
authors.initials: MC
authors.lastname: Field
authors.forename: David
authors.initials: D
authors.lastname: Horn
mesh_terms: D000818:Animals; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D013498:Suramin / Q000008:administration & dosage*; D022161:Transport Vesicles / Q000378:metabolism*; D014344:Trypanocidal Agents / Q000008:administration & dosage*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000378:metabolism; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000469:parasitology
chemical_list: D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; D013498:Suramin