meso-Substituted BODIPY rotors as lipid droplet probes for cell-type differentiation

Abstract

Cancer remains a leading cause of death worldwide despite advances in technology and therapeutics. Lipid droplets (LDs) have recently emerged as promising cancer biomarkers, as cancer cells typically exhibit a higher abundance and viscosity of LDs than normal cells. This has driven interest in developing small-molecule activatable fluorescent probes that respond to microenvironmental cues. Unlike conventional “always-on” probes, these systems enhance fluorescence response selectively in environments with altered viscosity, polarity, pH, or temperature minimizing background noise and enabling precise tracking of molecular processes within organelles. In this context, we have designed and synthesized two new BODIPY-based molecular rotors for LD targeting. The key difference between the two probes lies in their molecular conformation: compound 8 features tetramethyl groups on the indacene core, which significantly influence its optical properties. In contrast, compound 7 with more pronounced rotor dynamics shows higher sensitivity to viscosity variations. The photophysical properties are supported by DFT and TD-DFT calculations (B3LYP/6-31G(d,p), Gaussian 09W). Both probes demonstrate low cytotoxicity, good photostability, and excellent LD selectivity, allowing clear distinction between normal and cancerous cells.