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

Amorphous magnesium-substituted calcium phosphate (AMCP) nanoparticles (75-150 nm) 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 5 nm 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.

Graphical AbstractAmorphous magnesium-substituted calcium phosphate (AMCP) nanoparticles, which form naturally in the mammalian gut, may play an important role in immune surveillance by promoting the delivery of luminal macromolecules to mucosal immune cells. To further probe this constitutive phenomenon, we set out to develop a synthetic mimetic generating in vitro amorphous calcium phosphate nanoparticles similar to their in vivo counterparts. Resulting synthetic particles were of the right size (75-150 nm), phase (amorphous) and composition (magnesium-substituted calcium phosphate) and trapped macromolecules effectively delivering them to antigen presenting cells without adverse effects. The silent delivery of macromolecules by synthetic AMCP informs on their in vivo role and could be exploited as a safe platform for antigen delivery.129