ADME Profiling of Quantum Dots and Immune Responses: Impact of Dynamic Inflammatory Mediator Changes on the Nervous System

ABSTRACT Cadmium telluride (CdTe) quantum dots (QDs) show great potential for biomedical applications owing to their excellent optical properties. Nevertheless, concerns about their potential neurotoxicity remain unanswered. Here, we conduct a systematic assessment. We study the biodistribution, neurobehavioral effects, and cellular responses in mice after tail vein injection of mercaptopropionic acid–modified CdTe QDs. The QDs display a blood clearance half‐life of around 8 h. They mainly accumulate in the liver and kidneys and cross the blood–brain barrier within one hour, with the highest accumulation within the brain regions. Significantly, even though there is transient systemic toxicity, exposure to QDs triggers persistent neuroinflammation and causes substantial impairments in hippocampus‐dependent learning and memory. To clarify the underlying mechanisms, we carried out single‐cell RNA sequencing on hippocampal tissue. This high‐resolution analysis uncovers a coordinated multicellular response, with microglia, oligodendrocyte precursors, and endothelial cells serving as key contributors to inflammatory, oxidative, and cellular stress pathways. These findings clarify the multicellular mechanisms underlying QD‐induced neurotoxicity and establish a framework for assessing the neuro‐safety of nanomaterials in biomedical settings.