Tea-derived natural nanodrug simultaneously enables real-time fluorescent tracking and noninvasive treatment of neuroinflammation in Alzheimer's disease.

Neuroinflammation and glutamate-induced excitotoxicity are key drivers of synaptic dysfunction and cognitive decline in Alzheimer's disease (AD). However, chemically synthesized small-molecule drugs (e.g., memantine) often cause potential dose-dependent neurotoxicity, limited inflammation-targeting capability, and rapid systemic clearance, resulting in suboptimal therapeutic efficacy. Here, we introduce a tea-derived multifunctional natural nanodrug that enables real time fluorescence tracking and noninvasive treatment of neuroinflammation in AD. The natural nanodrug is derived from Pu-erh tea leaves, formulated with memantine and biomimetic vesicles for intranasal nebulized delivery. The tea-derived biomimetic nanodrug features intrinsic fluorescence, enabling real-time tracking at both cellular and tissue levels, with preferential colocalization in activated microglia and selective accumulation in neuroinflammatory brain regions. Remarkably, under matched nebulization conditions and nominal memantine loading, the tea-derived natural nanodrug shows an improved safety and efficacy relative to free memantine, significantly improving behavioral outcomes and reducing hippocampal damage. This noninvasive strategy enables efficient brain targeting and markedly restores hippocampal structure and cognitive performance in AD mouse models. Together, our study suggests new avenues and exciting opportunities for developing natural nanodrugs for noninvasively and precisely treating brain diseases including but not limited to AD.