title: Synthetic mimetics of the endogenous gastrointestinal nanomineral: Silent constructs that trap macromolecules for intracellular delivery.
abstract: Amorphous magnesium-substituted calcium phosphate (AMCP) nanoparticles (75-150nm) form constitutively in large numbers in the mammalian gut. Collective evidence indicates that they trap and deliver luminal macromolecules to mucosal antigen presenting cells (APCs) and facilitate gut immune homeostasis. Here, we report on a synthetic mimetic of the endogenous AMCP and show that it has marked capacity to trap macromolecules during formation. Macromolecular capture into AMCP involved incorporation as shown by STEM tomography of the synthetic AMCP particle with 5nm ultra-fine iron (III) oxohydroxide. In vitro, organic cargo-loaded synthetic AMCP was taken up by APCs and tracked to lysosomal compartments. The AMCP itself did not regulate any gene, or modify any gene regulation by its cargo, based upon whole genome transcriptomic analyses. We conclude that synthetic AMCP can efficiently trap macromolecules and deliver them to APCs in a silent fashion, and may thus represent a new platform for antigen delivery.
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK.
authors.forename: Laetitia C
authors.initials: LC
authors.lastname: Pele
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK.
authors.forename: Carolin T
authors.initials: CT
authors.lastname: Haas
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Hewitt
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Robertson
authors.affiliation: Cambridge advanced Imaging Centre, Physiology development and Neuroscience, Anatomy building, University of Cambridge, Cambridge.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Skepper
authors.affiliation: Institute for Materials Research, SCAPE, University of Leeds, Leeds.
authors.forename: Andy
authors.initials: A
authors.lastname: Brown
authors.affiliation: Departamento de Ciencia de los Materiales e Ingeniería Metalúrgica y Química Inorgánica, Facultad de Ciencias, Universidad de Cádiz, Campus Universitario Rio San Pedro, Puerto Real, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Hernandez-Garrido
authors.affiliation: Department of Materials Science and Metallurgy, University of Cambridge, Cambridge.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Midgley
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK.
authors.forename: Nuno
authors.initials: N
authors.lastname: Faria
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Chappell
authors.affiliation: Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK. Electronic address: jonathan.powell@mrc-hnr.cam.ac.uk.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Powell
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells; D000941:Antigens; D003593:Cytoplasm; D046911:Macromolecular Substances; D053758:Nanoparticles
chemical_list: D000941:Antigens; D046911:Macromolecular Substances
keywords: Amorphous magnesium-substituted calcium phosphate; Nanoparticles; PD-L1; Peptidoglycan