A Nature-Inspired Steroid-like Electron Acceptor to Polarity-Dependent Probe for Visualizing Lipid Evolution in Alzheimer’s Disease

Current petrochemical-based electron acceptors in advanced
optical
materials face problems such as structural diversity, renewability,
and biocompatibility. Natural product-derived fluorescent materials
with donor–acceptor structures, stimuli-responsive photophysical
properties, and superior biocompatibility are crucial for biomedical
applications like visualizing the lipid evolution in Alzheimer’s
disease (AD). In this work, a nature-inspired electron acceptor (DABT)
analogous to steroids has been constructed based on the tricyclic
diterpene skeleton of natural rosin. Through substitution with variable
electron donors, the dimethyl amino-substituted compound, DABT-DMA,
can be applied as a polarity-dependent biosensor with dual-stimuli
responsiveness of distinct fluorescence wavelength and lifetime. The
natural skeleton’s advantageous biocompatibility and targeting
capability enable lipid droplet-targeted imaging. Further investigations
prove that the single biobased sensor can combine the bilateral advantages
of two commercial probes, confirming that Aβ protein-induced
lipid droplet dysfunction causes cholesterol analogue accumulation,
worsening AD pathology. This work not only proposes a steroid-like
natural electron acceptor with both biocompatibility and targeting
capability but also offers insights into AD-related pathophysiological
mechanisms.