Intrauterine inflammation increases materno-fetal transfer of gold nanoparticles in a size-dependent manner in murine pregnancy

The materno-fetal transfer of nanoparticles is a critical issue in designing theranoustic nanoparticles for in vivo applications during pregnancy. Recent studies have reported that certain nanoparticles can cross the placental barrier in healthy pregnant animals depending on the size and surface modification of the nanoparticles and the developmental stages of the fetuses. However, materno-fetal transfer under pathological pregnant conditions has not been examined so far. Here, it is shown that intrauterine inflammation can enhance the materno-fetal transfer of nanoparticles in the late gestation stage of murine pregnancy in a size-dependent manner. Three different-sized gold nanoparticles (Au NPs) with diameters of 3 (Au3), 13 (Au13) and 32 (Au32) nm are applied. The accumulation of Au3 and Au13 nanoparticles in the fetuses is significantly increased in intrauterine inflammatory mice compared with healthy control mice: the concentration of Au3 is much higher than Au13 in fetal tissues of intrauterine inflammatory mice. In contrast, Au32 nanoparticles cannot cross the placental barrier either in healthy or in intrauterine inflammatory mice. The possible underlying mechanism of the increased materno-fetal transfer of small-sized nanoparticles on pathological conditions is inferred to be the structural and functional abnormalities of the placenta under intrauterine inflammation. The size of the nanoparticles is one of the critical factors which determines the extent of fetal exposure to nanoparticles in murine pregnancy under inflammatory conditions.