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

Abstract

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 (nπ*) configuration. All nS-PDIs are non-emissive in solution but reveal an excellent twophoton absorption cross-section of >800 GM. Supported by the femtosecond transient absorption study, the S 1 (nπ*) → 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.

Site-selected thionated benzothioxanthene chromophores as heavy-atom-free small-molecule photosensitizers for photodynamic therapy

“…In aqueous solution, BTI , T1 , T2 , and T3 showed the propensity to form nanoaggregates ( BTI = 316 nm, T1 = 100 nm, T2 = 172 nm, T3 = 151 nm) in line with previously published data reporting on the use of thionaphthalimides 37 or thione-derived perylene diimides 41 as activated-self-assembled PSs (Supplementary Fig. 20 ).…”

“…20 ). It is important to note that the propensity of self-assembled dyes to disaggregate into monomeric units upon binding to biological targets in cell culture conditions has been used in both biosensing 54 – 57 and therapeutic applications 37 , 41 , 58 . This would be a particularly important expected feature in the present study, as we already mentioned that no singlet-oxygen or other ROS generation could be monitored in aqueous media, while singlet oxygen and superoxide generation could be attested in chloroform and DMSO, respectively.…”

“…Site-selected thionation in the PS´ scaffold is another even more recent approach used to impart unique structural, photochemical, and therapeutic outcomes 26 , 37 – 41 . Indeed, Yoon´s group reported on the use of thionaphthalimides as efficient ROS generators under both normoxia and hypoxia conditions 37 .…”

“…Indeed, Yoon´s group reported on the use of thionaphthalimides as efficient ROS generators under both normoxia and hypoxia conditions 37 . Even more recently, Chou and co-workers reported on the use of thione-derived perylene diimides as promising PDT agents 41 .…”

Why does thionating a carbonyl molecule make it a better electron acceptor?

“…This photosensitisation process can be achieved using site-selectively modified nucleobases or synthetic chromophores with heavy-atom-free thiocarbonyl functionalities. [7][8][9][10] Given the long lifetime and high energy of the triplet excited states, thiocarbonyl chromophores also display photocatalytic activities comparable to common organometallic photocatalysts. 11 For materials applications, Seferos and co-workers reported that the carrier mobility of n-type organic field-effect transistors (OFET) based on perylene diimide derivatives can be enhanced by thionation.…”