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

Abstract Reactive oxygen species (ROS) are crucial in photodynamic therapy (PDT), but their generation is highly dependent on the S‐T bandgap (Δ E 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 Δ E 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.