- The full article entitled “Comprehensive Thione-Derived Perylene Diimides and Their Bio-Conjugation for Simultaneous Imaging, Tracking, and Targeted Photodynamic Therapy” can be found at the JACS website at https://pubs.acs.org/doi/full/10.1021/jacs.2c07967
- Authors: Yao-Lin Lee, Yi-Te Chou, Bo-Kang Su, Chi-chi Wu, Chih-Hsing Wang, Kai-Hsing Chang, Ja-an Cnnie Ho*, and Pi-Tai Chou*
Photodynamic therapy has proved to be an effective way for cancer treatment due to its non-invasive, spatiotemporal and inexpensive methodology. However, it is short of extensive application owing to shallow light penetration, insufficient oxygen dependence and lack of selectivity on cancer cells. A research team led by Prof. Chou and Prof. Ho in the Department of Chemistry, NTU designed a series of 3,4,9,10-perylenetetracarboxylic diimide based derivatives. After thionation, new thiol-compounds named as 1S-PDI-D, 2S-cis-PDI-D, 2S-trans-PDI-D, 3S-PDI-D and 4S-PDI-D denoted as 1-4 thione moieties, respectively, were synthesized. The observed prominent lower-lying absorption for all derivatives is assigned to the S0 → S2 (ππ*) transition and is red-shifted upon increasing the number of thiones. They all possess high two-photon absorption cross section and unity triplet state population upon excitation and are potential to be ideal photosensitizers. Their singlet oxygen yield order to be 1S-PDI-D (~100%) > 2S-cis-PDI-D > 2S-trans-PDI-D >> 3S-PDI-D = 4S-PDI-D (~0%). This abnormal phenomenon is rationalized by theoretical calculation, where lowest-lying T1 (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 T1 energy of 1S-PDI-D (1.10 eV) is higher than that (0.97 eV) of the 1O2, 1Δg state. 1S-PDI-D having excellent photosensitization capability was 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 mouse., where Cy5-1S-FC131 shows superiority of simultaneous fluorescence tracking and targeted photodynamic therapy. Therefore, the targeting, therapeutic, and imaging function of Cy5-1S-FC131 enables itself to serve as a promising curative probe in tumor precision medicine.
