Comprehensive Thione-Derived Perylene Diimides and Their Bio-Conjugation for Simultaneous Imaging, Tracking, and Targeted Photodynamic Therapy.

In this study, the chromophore 3,4,9,10-perylenetetracarboxylic diimide (PDI) is anchored with phenyl substituents at the imide N site, followed by thionation, yielding a series of thione products 1S-PDI-D , 2S- cis -PDI-D , 2S- trans -PDI-D , 3S-PDI-D , and 4S-PDI-D , respectively, with n = 1, 2, 3, and 4 thione. The photophysical properties are dependent on the number of anchored thiones, where the observed prominent lower-lying absorption is assigned to the S 0 → S 2 (ππ*) transition and is red-shifted upon increasing the number of thiones; the lowest-lying excited state is ascribed to a transition-forbidden S 1 ( n π*) configuration. All n S-PDI s are non-emissive in solution but reveal an excellent two-photon absorption cross-section of >800 GM. Supported by the femtosecond transient absorption study, the S 1 ( n π*) → T 1 (ππ*) intersystem crossing (ISC) rate is > 10 12 s -1 , resulting in ∼100% triplet population. The lowest-lying T 1 (ππ*) energy is calculated to be in the order of 1S-PDI-D > 2S- cis -PDI-D ∼ 2S- trans -PDI-D > 3S-PDI-D > 4S-PDI-D , where the T 1 energy of 1S-PDI-D (1.10 eV) is higher than that (0.97 eV) of the 1 O 2 1 Δ g state. 1S-PDI-D is further modified by either conjugation with peptide FC131 on the two terminal sides, forming 1S-FC131 , or linkage with peptide FC131 and cyanine5 dye on each terminal, yielding Cy5-1S-FC131 . In vitro experiments show power of 1S-FC131 and Cy5-1S-FC131 in recognizing A549 cells out of other three lung normal cells and effective photodynamic therapy. In vivo, both molecular composites demonstrate outstanding antitumor ability in A549 xenografted tumor mice, where Cy5-1S-FC131 shows superiority of simultaneous fluorescence tracking and targeted photodynamic therapy.