Lipid Droplet-Targeted BODIPY–Hemicyanine Hybrid Fluorescent Probes for Real-Time Monitoring of pH and Viscosity

Lipid droplets (LDs) are pivotal organelles in lipid
metabolism,
whose dysfunction links to atherosclerosis and cancer. Microenvironmental
factors, like microviscosity and pH, are closely linked to various
pathophysiological processes. However, single-parameter diagnostic
tools fall short of comprehensive assessments of diseases. To address
this challenge, we have developed a novel multifunctional fluorescent
probe series, LD-VP, by fusing a BODIPY core with hydroxyethyl-substituted
hemicyanine moieties via an ethylene bond. These hybrids can selectively
target LDs while detecting viscosity (via restricted molecular rotations
to enhance red fluorescence) and pH (via disrupting the hemicyanine
structure, causing blue-shifted emission under alkaline conditions).
Notably, LD-VP1 can successfully discriminate tumor cells
from normal cells and effectively reveals pathological LD features
(increased quantity, size, and viscosity with stable pH) during atherosclerotic
foam cell formation. This work successfully demonstrates the practical
value of multifunctional probes for understanding and diagnosing complex
diseases, offering a stellar example for the advancement of multifunctional
probe development.