Viscosity-responsive AIEgen with mitochondrial/endoplasmic reticulum dual targeting for fatty liver fluorescence imaging and tumor photodynamic therapy.

Combining quantum chemical calculations with molecular dynamics simulations, we rationally designed a near-infrared (NIR) viscosity-responsive aggregation-induced emission luminogen (AIEgen), TTPL3, via π-conjugated bridge modulation and acceptor-terminal hydroxylation, with dual targeting to mitochondria and endoplasmic reticulum. Under white light irradiation, TTPL3 showed excellent reactive oxygen species (ROS) generation efficiency and remarkable photodynamic therapeutic (PDT) activity against 4 T1 breast cancer cells. Its fluorescence intensity increased by 15.03-fold as viscosity rose from 0.63 cP to 1281 cP, showing prominent viscosity responsiveness. Colocalization experiments confirmed TTPL3's precise dual organelle targeting in MDA-MB-231 cells, with Pearson's correlation coefficients of 0.94 and 0.96. TTPL3 was applicable for fatty liver fluorescence imaging and induced tumor cell apoptosis via the mitochondrial apoptotic pathway. In vivo studies showed TTPL3 achieved efficient tumor phototherapy with a 50.38% inhibition rate, indicating it is a promising AIE-based platform for integrated fatty liver diagnosis and tumor phototherapy.