Dual-emissive self-reporting photosensitizers characterized by Kasha/anti-Kasha behaviors engineered via a gradient donor-acceptor strategy

Abstract

Real-time monitoring of photodynamic therapy (PDT) is essential for precision medicine, yet remains hindered by microenvironmental interference and photobleaching of conventional mono-emissive photosensitizers (PSs). Herein, inspired by the energy level gradients depicted in the Jablonski diagram, we report a gradient donor-acceptor molecular design strategy to overcome Kasha's rule, achieving intrinsic dual-emissive PSs. Combining femtosecond transient absorption spectroscopy with theoretical calculations, we have verified the Kasha/anti-Kasha properties of the compounds: near-infrared (NIR) emission peaking at 710 nm, exhibiting viscosity dependence stems, from the S1-to-S0 excited-state decay of the primary acceptor-donor framework, whereas visible emission at 530-590 nm, significantly enhanced upon DNA binding, originates from the S2-to-S0 excited-state decay of the additional acceptor-donor segment. A systematic comparison of the effects of additional acceptors on anti-Kasha behaviors and photogenerated reactive oxygen species (ROS) performance has been conducted by constructing two diketopyrrolopyrrole (DPP)-based isomers, namely DPP-F32 and DPP-F34. Both PSs target the Golgi apparatus to activate NIR signals, but only DPP-F32 exhibits visible emission in the nucleus of apoptotic cells, enabling ratiometric tracking of the PDT process at two-/three-dimensional cellular models via dual-channel imaging. This study provides a new paradigm for self-reporting PSs with Kasha/anti-Kasha behaviors that combine precise targeting, efficient ROS generation, and real-time dynamic monitoring.