Recently, several disorders of the central nervous system (CNS), including Alzheimer's disease (AD) and neuroinflammation have been associated with dysfunction of the neurovascular unit (NVU). As a result, there is an increased demand for therapeutic tools able to act at the NVU. We studied liposomes functionalized with apolipoprotein-E and phosphatidic acid (mApoE-PA-LIP), previously used to promote Aβ removal across the blood-brain barrier (BBB) in an in vivo model of AD, with memory improvement. We performed calcium imaging to study ATP-evoked intracellular Ca2+ waves in hCMEC/D3 and in astrocytes and electrophysiological recordings to assess whether mApoE-PA-LIP can also modulate the neuronal synaptic transmission. Our results show that mApoE-PA-LIP increased the ATP-evoked intracellular Ca2+ waves and increased sEPSCs frequency, giving additional support to promote them as putative therapeutic tool for AD treatment. Since it has been demonstrated that the inhalation of airborne particulate matter (PM) may contribute to the neurodegeneration onset and progression, understanding the inner mechanisms related to PM exposure is fundamental to develop strategies to limit neurodegenerative processes. By means of nanomedicine and nanotoxicology approaches, the synergistic employment of in vivo and in vitro techniques to study the NVU dysfunctions will shed a light on the vascular risks that can affect the endothelium thus triggering the neurodegeneration and neuroinflammation.