A nature-inspired steroid-like electron acceptor to polarity-dependent probe for visualizing lipid evolution in Alzheimer’s disease

To date, most optical materials are derived from petrochemicals, facing problems like renewability, sustainability, and biocompatibility. Fluorescent materials derived from natural products with unique structures, stimuli-responsive photophysical properties, and superior compatibility are of extraordinary significance for biomedical applications. In this work, a nature-inspired electron acceptor with a steroid-like structure (DABT) has been constructed based on the tricyclic diterpene skeleton of natural rosin. Through substitution with variable electron donors, red-shifted and twisted intramolecular charge transfer can be realized. In particular, the dimethyl amino substituted compound, DABT-DMA, can be applied as a polarity-dependent bio-sensor with a dual responsiveness of distinct fluorescence wavelength and lifetime due to its outstanding solvent effect. In addition to the advantageous biocompatibility and steroid-like structure of DABT-DMA, successful lipid droplet-targeted imaging at dual channels can be achieved. Further investigations prove that dysfunction of lipid droplets induced by Aβ protein can result in the accumulation of cholesterol analogs, further exacerbating the pathological features of Alzheimer’s disease. This work not only proposes a novel natural electron acceptor with a steroid-like structure possessing both biocompatibility and targeting capability but also offers new insights into Alzheimer’s disease-related pathophysiological mechanisms, paving the way toward potential diagnostics.