Semiconducting Open‐Shell Radicals for Precise Tumor Activatable Phototheranostics

Semiconducting open-shell radicals (SORs) have promising potential for the development of phototheranostic agents, enabling tumor bioimaging and boosting tumorous reactive oxygen species (ROS). Herein, a new class of semiconducting perylene diimide (PDI), designated as PDI(Br)_n with various numbers of bromine (Br) atoms modified on PDI's bay/ortho positions is reported. PDI(Br)_n is demonstrated to transform into a radical anion, [PDI(Br)_n]^•-, in a reducing solution, with a typical g-value of 2.0022. Specifically, [PDI(Br)_4/6]^•- is generated in the weakly reductive tumor-mimicking solution and exhibits high stability in air. Quantum chemical kinetic simulation and ultrafast femtosecond transient absorption spectroscopy indicate that [PDI(Br)₆]^•- has a low π-π stacking energy (0.35 eV), a fast electron transfer rate (192.4 ps) and energy gap of PDI(Br)₆ (ΔE_{S1, T1}= 1.307 eV, ΔE_{S1, T2}= 0.324 eV) respectively, which together result in excited-state charge transfer characters. The PDI(Br)₆ nanoparticle radicals, [PDI(Br)₆] NPs^•-, specifically enable chemodynamic and type-I photodynamic ROS generation in tumors, including superoxide and hydroxyl radicals, which elicit immunogenic cell death effect. Also, [PDI(Br)₆] NPs^•- facilitate activatable bioimaging-guided therapy due to their photoacoustic signal at 808 nm and NIR-II emission at 1115 nm. The work paves the way for the design of SORs for precise cancer theranostics.