Nanoplastic Translocation Across Biological Barriers (Blood-Brain, Placental, Intestinal): Transport Mechanisms, Tissue-Specific Vulnerabilities, and a Corona-Driven Barrier Selectivity Framework

Nanoplastics (NPs; <= 1 & micro;m) have been detected in human placenta, blood, lung, atherosclerotic plaque, testis, semen, olfactory bulb, and brain, shifting the field from environmental description toward mechanistic interrogation of barrier crossing. This review synthesises current evidence on NP translocation across the intestinal epithelium, the blood-brain barrier (BBB) and the placental syncytiotrophoblast. We distinguish four evidence categories throughout the review: detection, association, mechanism, and causality. We also apply model-system labels (in silico, in vitro, ex vivo, animal, and human) to every mechanistic claim, so that the strength of each statement can be read off directly. Most current studies use pristine polystyrene nanoplastics at concentrations 3-6 orders of magnitude above plausible human exposure, so the mechanistic conclusions below are hypothesis-generating for human disease rather than definitive. We propose a working conceptual framework-corona-driven barrier selectivity (CDBS)-in which the particle-corona-surface complex, rather than the bare polymer, is hypothesised to dictate which receptor and transport machinery (TfR1, LRP1, FcRn, P-gp/BCRP, caveolae) each barrier engages. CDBS is offered as a hypothesis-stage organising tool requiring experimental validation, not as an established mechanism. We outline reported transport modes, including clathrin- and caveolin-mediated endocytosis, paracellular leakage via ROS-induced tight-junction disassembly, receptor-mediated transcytosis, and the candidate olfactory route. We emphasise that pristine polystyrene-bead doses commonly exceed plausible human exposure by 3-6 orders of magnitude, that detection methods underestimate sub-micrometre particles, and that causal links between NPs and human disease remain hypothesis-generating. A research agenda built on weathered reference materials, microphysiological systems, and integrative human biomarker science is proposed.