Synthesis, Two-photon Fluorescence Imaging and Photodynamic Therapy of Near Infrared Thienyl-BODIPY Photosensitizer
Received date: 2022-04-01
Online published: 2022-06-20
Supported by
National Natural Science Foundation of China(62075039)
In this paper, two novel thienyl boron dipyrromethene (thienyl-BODIPY) near infrared (NIR) photosensitive dyes, ITBDP-1 and ITBDP-2 were designed and synthesized. The absorption and emission wavelengths of two photosensitizers reach near infrared region. The absorption and emission peaks of ITBDP-1 are 617 and 650 nm while the absorption and emission peaks of ITBDP-2 are 687 and 731 nm respectively. The singlet oxygen yields (ΦΔ) of photosensitizers were determined using 1,3-diphenyliso- benzofuran (DPBF) as singlet oxygen scavenger. The results turned out that two photosensitizers both could generate singlet oxygen under 660 nm light irradiation, and the absorption of DPBF decreased over 50% within 1 min. ΦΔ of ITBDP-1 and ITBDP-2 are 51% and 24% respectively. Excited state energy level of photosensitizers were studied by density functional theory (DFT) calculation. Theoretical calculation indicates that ITBDP-1 and ITBDP-2 can reach triplet state through intersystem crossing (ISC) after being excited to singlet state, thus improving singlet oxygen yield. ITBDP-1 and ITBDP-2 showed satisfying imaging effect in A549 cells, and ITBDP-1 could show distinct two-photon fluorescence in zebrafish under 900 nm excitation. Apart from good cell imaging effect, these two photosensitizers showed abilities to generate reactive oxygen species (ROS) in tumor cells as well. It can be proved that photosensitizers could produce singlet oxygen in tumor cells and zebrafish under light excitation with dichlorodihydrofluorescein diacetate (DCFH-DA) as ROS indicator. Besides, ITBDP-1 and ITBDP-2 also presented high cytotoxicity under 660 nm light irradiation. In the tetrazolium (MTT) experiment, the maximum half inhibitory concentration (IC50) of ITBDP-1 and TBDP-2 were 2.22 and 2.86 μmol•L-1 respectively, and the cell viability was over 80% without irradiation, which proved that both photosensitizers possess high phototoxicity and good biocompatibility. ITBDP-1 and ITBDP-2 could realize imaging-guided photodynamic therapy under excitation of NIR light in tumor cells, and displayed two-photon fluorescence imaging in vivo. Photosensitizers ITBDP-1 and ITBDP-2 are excepted to lay good foundation for the application of thienyl-BODIPY photosensitizers in two-photon photodynamic therapy under NIR excitation.
Badi Liu , Chengjun Wang , Ying Qian . Synthesis, Two-photon Fluorescence Imaging and Photodynamic Therapy of Near Infrared Thienyl-BODIPY Photosensitizer[J]. Acta Chimica Sinica, 2022 , 80(8) : 1071 -1083 . DOI: 10.6023/A22040141
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