Nanoplastics perturb extracellular vesicle-mediated communication in the in vitro and ex vivo bone marrow microenvironment of multiple myeloma

Nanoplastics (NPs) are emerging environmental contaminants capable of interacting with biological systems, yet their effects on intercellular communication in the bone marrow (BM) microenvironment remain unclear. This study investigated the impact of polystyrene NPs on extracellular vesicle (EV) biogenesis, cargo, and function using in vitro models of multiple myeloma (MM) and stromal cells, supported by ex vivo murine bone and human BM aspirates. Under the experimental conditions used in this study, NPs were efficiently internalized by both malignant and stromal cells, inducing oxidative stress and reducing cell viability. NP exposure altered EV biogenesis, leading to increased vesicle release, reduced size, and the incorporation of NPs into a subset of EVs. Additionally, EVs from NP-exposed MM cells showed decreased total miRNA content and modulation of miRNA sorting-related proteins. Among the analyzed miRNAs, miR-505, a candidate linked to osteogenic regulation, was reduced in both cells and EVs following NP exposure. Functionally, EVs from control MM cells downregulated osteogenic markers in pre-osteoblasts, whereas EVs from NP-exposed cells showed reduced regulatory effects. These findings demonstrate that NP exposure modifies EV-mediated signaling under experimental conditions, providing mechanistic insight into nanoplastic interference with BM cellular communication.