A Thienyl‐Substituted Diketopyrrolopyrrole Derivative with Efficient Reactive Oxygen Species Generation for Photodynamic Therapy

Reducing the energy gap of photosensitizer between singlet and triplet states (Delta E-ST) can improve the efficiency of intersystem crossing, further enhancing the resulting generation of reactive oxygen species for photodynamic therapy. In this study, two photosensitizer chromophores-phenyl-substituted diketopyrrolopyrrole and thienyl-substituted diketopyrrolopyrrole (TDPP)-were synthesized. Theoretical calculations indicate that TDPP can greatly reduce the Delta E-ST (0.48 eV) relative to that of diketopyrrolopyrrole (0.66 eV). Experiments confirmed that TDPP generates reactive oxygen species more efficiently than diketopyrrolopyrrole. After conjugation of TDPP with methoxy poly(ethylene glycol) carboxyl (mPEG-COOH), the resulting TDPP-mPEG has excellent water solubility, biocompatibility and photostability. When it serves as photosensitizer for photodynamic therapy, in vitro and in vivo measurements indicate that TDPP-mPEG can effectively inhibit tumor growth and shows great potential for the treatment of cancer in the clinic.