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Synthetic mimetics of the endogenous gastrointestinal nanomineral: Silent constructs that trap macromolecules for intracellular delivery.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Pele, Laetitia C 
Haas, Carolin T 
Hewitt, Rachel E 
Robertson, Jack 
Skepper, Jeremy 

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.

Description

Keywords

Amorphous magnesium-substituted calcium phosphate, Nanoparticles, PD-L1, Peptidoglycan, Animals, Antigen-Presenting Cells, Antigens, Cytoplasm, Macromolecular Substances, Nanoparticles

Journal Title

Nanomedicine

Conference Name

Journal ISSN

1549-9634
1549-9642

Volume Title

13

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MR/R005699/1)