Turning Lemons into Lemonade: One‐Step Synthesized Dual‐Acceptor Organic Photosensitizer to Boost the Photodynamic Therapy

Reactive oxygen species (ROS) are crucial in photodynamic therapy (PDT), but their generation is highly dependent on the S-T bandgap (ΔE_ST), spin-orbit coupling (SOC), intersystem crossing rate (k_ISC), and also excited triplet-states lifetime (τ_Triplet) in organic photosensitizers (PSs). In contrast to the widely reported donor-acceptor-donor (D-A-D) type PSs, D-A-A-D typed PSs are seldomly developed for the time-consuming and complicated synthesis, but show great potential in enhancing ROS generation in phototheranostics. This work here presents a one-step synthetic procedure of D-A-A-D type 2DMeTPA-2BT with a high yield of 47%, which is significantly different from the previously reported dual-acceptor cases. In contrast to 2DMeTPA-BT, the dual-acceptor PSs of 2DMeTPA-2BT display a much smaller ΔE_ST value but large SOC constants. Also, the intersystem crossing (ISC) dynamics indicate that fast k_ISC, long τ_Triplet, and large triplet population are observed in 2DMeTPA-2BT-based nanoparticles (NPs), contributing to a superior generation of ROS. 2DMeTPA-2BT NPs are then finally utilized for the imaging-guided PDT in vivo with a tumor inhibition rate of 90%. This method offers an efficient way to produce dual-acceptor typed PSs via a one-step reaction, providing new avenues in high-performance phototheranostics.