Mammary Leukocyte‐Assisted Nanoparticle Transport Enhances Targeted Milk Trace Mineral Delivery

Abstract Nanoparticles are applied as versatile platforms for drug/gene delivery in many applications owing to their long‐retention and specific targeting properties in living bodies. However, the delivery mechanism and the beneficial effect of nanoparticle‐retention in many organisms remain largely uncertain. Here, the transport and metabolism of mineral nanoparticles in mammary gland during lactation are explored. It is shown that maternal intravenous administration of iron oxide nanoparticles (IONPs; diameter: ≈11.0 nm, surface charge: −29.1 mV, surface area: 1.05 m² g⁻¹) provides elevated iron delivery to mammary gland and increased iron secretion into breast milk, which is inaccessible by classical iron‐ion transport approaches such as the transferrin receptor‐mediated endocytic pathway. Mammary macrophages and neutrophils are found to play dominant roles in uptake and delivery of IONPs through an unconventional leukocyte‐assisted iron secretion pathway. This pathway bypasses the tight iron concentration regulation of liver hepcidin‐ferroportin axis and mammary epithelial cells to increase milk iron‐ion content derived from IONPs. This work provides keen insight into the metabolic pathway of nanoparticles in mammary gland while offering a new scheme of nutrient delivery for neonate metabolism regulation by using nanosized nutrients.