Nanomaterial's interfacial stimulation of vascular endothelial cells and divergent guidances for nanomedicine treating vasculature-associated diseases

Blood vasculature plays an essential role in transporting nanomaterials in vivo. However, the interaction between vascular endothelial cells (VECs) and nanomaterials lacked deep understanding, impeding the development of safe and efficient nanomedicine. Here, we discover that VECs can be significantly stimulated by two-dimensional PEGylated lamellar materials (PLMs) without being internalized. Additional experiments and computational simulations suggest that the unique VEC stimulation can be ascribed to the interaction between the PLMs and the membrane lipids, which induces ion-transport-related conformational change of L-type calcium ion channel Cav1.3. Additionally, the in vivo studies demonstrate that PLMs-stimulated VECs have divergent impacts on two types of vasculature-associated diseases: exacerbating the development of atherosclerosis while magnifying the accumulation of nanomedicine within tumors. Thus, the current study not only advances our understanding of how specific proteins on VEC membranes could be stimulated by PLMs but also guides the rational use of promising PLMs in nanomedicine.