A pH-responsive fluorescence nanosystem for imaging lipid deposition in diseased aortic valves

Lipid deposition is closely related to the pathogenesis of valvular heart disease (VHD), which is a potential target for the early diagnosis of VHD. However, early diagnosis of VHD and heart valve-specific delivery of imaging or therapeutic agents remain challenging. In this work, we hypothesized that lipid droplet-specific probe-loaded nanoparticles simultaneously responsive to the acidic pH of the lysosomes could be used as an effective nanosystem for the precise delivery of probes to the diseased aortic valves in which the endothelial layer was damaged. A lipid droplet-specific probe, namely, ECNBD, was synthesized and it showed great lipid-enhanced emission and great cellular and tissular lipid droplet-specific imaging capacity. Meanwhile, lysosome acid pH-responsive amphiphilic PEG-P (AEMA-<i>co</i>-PMA) was synthesized to serve as a nanocarrier for delivery of ECNBD. ECNBD-loaded nanoparticles exhibited good stability under physiological conditions, while the loaded probe was quickly released at pH 6.5. In addition, ECNBD-loaded nanoparticles could be internalized by cells, and the probe was quickly released because the acidic lysosome environment results in the lighting of intracellular lipid droplets. Impressively, ECNBD-loaded nanoparticles could accumulate in the diseased aortic valves of ApoE^-/- mice after tail vein injection and specifically stained the deposited lipid. Thus, our results demonstrated that ECNBD-loaded nanoparticles could serve as a potential nanoplatform for the diagnosis of VHD and the feasibility of diseased heart valve-targeted delivery of imaging or therapeutic agents.