Nanoplastics enhance F-53B uptake and synergistically induce colonic inflammation via activation of the B cell receptor pathway.

Nanoplastics (NPs) and microplastics (MPs) are ubiquitous environmental pollutants that act as carriers for persistent organic contaminants such as 6:2 chlorinated polyfluorinated ether sulfonic acid (F-53 B). This study investigated the biodistribution of orally administered 20 nm NPs and 2 μm MP, their interaction with F-53 B, and the intestinal toxicity of combined exposure. NPs showed higher bioavailability than MPs, with the intestine as the major accumulation site. In vitro, co-exposure to NPs and F-53 B exerted synergistic cytotoxicity in Caco-2 cells, whereas MPs showed no such effect, likely due to higher cellular uptake and cytotoxicity of NPs, along with their capacity to adsorb F-53 B, thereby enhancing its intracellular levels. In vivo, NPs elevated F-53 B levels in mouse plasma and colon, exacerbating colonic injury by increasing intestinal permeability, reducing mucin secretion, and upregulating IL-1β, TNF-α, and IL-6 expression. Single-cell RNA sequencing and in-vitro validation revealed that NPs and F-53 B co-exposure may activate BCR signaling pathway, increase intracellular Ca2+, and promote pro-inflammatory cytokines release via the NF-κB signaling pathway in intestinal B cells, promoting inflammatory-related damage. These findings indicate that NPs enhance F-53 B internal exposure and synergistically exacerbate intestinal injury, providing a foundation for assessing the health risks of NPs and co-existing environmental pollutants.