Benzo[a]phenoselenazine-based NIR Photodynamic Therapy for the Treatment of COX-2 Overexpressing Cancer Cells

Overview

Journal Future Med Chem

Specialties Chemistry
Pharmacy

Date 2025 Feb 15

PMID 39953784

Authors

Kalayou Hiluf Gebremedhin

Affiliations

Soon will be listed here.

Abstract

Background: Upregulation of Cyclooxygenase-2 (COX-2) in a variety of cancer cell lines, a key enzyme of prostaglandin biosynthesis, relative to surrounding normal tissues results in the use of the COX-2 protein as an attractive molecular target for many anticancer therapeutics. This could have a significant implication for selective destruction of cancer cells via the photodynamic therapy effects, leaving the normal tissue intact.

Experimental: Here, a COX-2-specific NIR photosensitizer (Se-C-IMC) was synthesized and developed by conjugating a classic anti-inflammatory drug indomethacin (IMC) as an efficient recognition group for COX-2 protein, with benzo[a]phenoselenazine derivative photosensitizer through hexanediamine linker.

Result And Discussion: In this study, Se-C-IMC exhibited a strong NIR absorption in the phototherapeutic window, relatively high O generation (Φ = 0.74 in CHC), and an excellent phototoxicity (IC = 0.04 µM, 14.4 J/cm) against MCF-7 cells as compared to COS-7 cells lacking COX-2 protein expression.

Conclusion: Se-C-IMC showed the highest intracellular localization in Golgi apparatus, making it to more effective for cellular destruction and Golgi targeted therapy. Thus, Se-C-IMC might hold great promise as a COX-2-specific NIR photosensitizer for improving the PDT efficiency and new Golgi-targeted PDT development in the future.

References

Murata H, Kawano S, Tsuji S, Tsuji M, Sawaoka H, Kimura Y . Cyclooxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma. Am J Gastroenterol. 1999; 94(2):451-5. DOI: 10.1111/j.1572-0241.1999.876_e.x. View

Uddin M, Crews B, Blobaum A, Kingsley P, Gorden D, McIntyre J . Selective visualization of cyclooxygenase-2 in inflammation and cancer by targeted fluorescent imaging agents. Cancer Res. 2010; 70(9):3618-27. PMC: 2864539. DOI: 10.1158/0008-5472.CAN-09-2664. View

Tian J, Ding L, Xu H, Shen Z, Ju H, Jia L . Cell-specific and pH-activatable rubyrin-loaded nanoparticles for highly selective near-infrared photodynamic therapy against cancer. J Am Chem Soc. 2013; 135(50):18850-8. DOI: 10.1021/ja408286k. View

Williams C, Tsujii M, Reese J, Dey S, DuBois R . Host cyclooxygenase-2 modulates carcinoma growth. J Clin Invest. 2000; 105(11):1589-94. PMC: 300858. DOI: 10.1172/JCI9621. View

Yuan A, Tang X, Qiu X, Jiang K, Wu J, Hu Y . Activatable photodynamic destruction of cancer cells by NIR dye/photosensitizer loaded liposomes. Chem Commun (Camb). 2015; 51(16):3340-2. DOI: 10.1039/c4cc09689d. View

Lanzo C, SUTIN J, Rowlinson S, Talley J, Marnett L . Fluorescence quenching analysis of the association and dissociation of a diarylheterocycle to cyclooxygenase-1 and cyclooxygenase-2: dynamic basis of cyclooxygenase-2 selectivity. Biochemistry. 2000; 39(20):6228-34. DOI: 10.1021/bi992761o. View

Li H, Gong Q, Luo K . Biomarker-driven molecular imaging probes in radiotherapy. Theranostics. 2024; 14(10):4127-4146. PMC: 11234278. DOI: 10.7150/thno.97768. View

Yogo T, Urano Y, Kamiya M, Sano K, Nagano T . Development of enzyme-activated photosensitizer based on intramolecular electron transfer. Bioorg Med Chem Lett. 2010; 20(15):4320-3. DOI: 10.1016/j.bmcl.2010.06.091. View

Uddin M, Crews B, Ghebreselasie K, Marnett L . Design, synthesis, and structure-activity relationship studies of fluorescent inhibitors of cycloxygenase-2 as targeted optical imaging agents. Bioconjug Chem. 2013; 24(4):712-23. PMC: 3630741. DOI: 10.1021/bc300693w. View

10.

Ziessel R, Allen B, Rewinska D, Harriman A . Selective triplet-state formation during charge recombination in a fullerene/Bodipy molecular dyad (Bodipy=borondipyrromethene). Chemistry. 2009; 15(30):7382-93. DOI: 10.1002/chem.200900440. View

11.

Lovell J, Liu T, Chen J, Zheng G . Activatable photosensitizers for imaging and therapy. Chem Rev. 2010; 110(5):2839-57. DOI: 10.1021/cr900236h. View

12.

Zhang H, Fan J, Wang J, Dou B, Zhou F, Cao J . Fluorescence discrimination of cancer from inflammation by molecular response to COX-2 enzymes. J Am Chem Soc. 2013; 135(46):17469-75. DOI: 10.1021/ja4085308. View

13.

Zheng X, Sallum U, Verma S, Athar H, Evans C, Hasan T . Exploiting a bacterial drug-resistance mechanism: a light-activated construct for the destruction of MRSA. Angew Chem Int Ed Engl. 2009; 48(12):2148-51. DOI: 10.1002/anie.200804804. View

14.

Hu P, Wang R, Zhou L, Chen L, Wu Q, Han M . Near-Infrared-Activated Upconversion Nanoprobes for Sensitive Endogenous Zn Detection and Selective On-Demand Photodynamic Therapy. Anal Chem. 2017; 89(6):3492-3500. DOI: 10.1021/acs.analchem.6b04548. View

15.

Basmaciyan L, Azas N, Casanova M . Calcein+/PI- as an early apoptotic feature in Leishmania. PLoS One. 2017; 12(11):e0187756. PMC: 5675397. DOI: 10.1371/journal.pone.0187756. View

16.

El-Khouly M, Amin A, Zandler M, Fukuzumi S, DSouza F . Near-IR excitation transfer and electron transfer in a BF2-chelated dipyrromethane-azadipyrromethane dyad and triad. Chemistry. 2012; 18(17):5239-47. DOI: 10.1002/chem.201103074. View

17.

Fujita T, Matsui M, Takaku K, Uetake H, Ichikawa W, Taketo M . Size- and invasion-dependent increase in cyclooxygenase 2 levels in human colorectal carcinomas. Cancer Res. 1998; 58(21):4823-6. View

18.

Dougherty T, Gomer C, Henderson B, Jori G, Kessel D, Korbelik M . Photodynamic therapy. J Natl Cancer Inst. 1998; 90(12):889-905. PMC: 4592754. DOI: 10.1093/jnci/90.12.889. View

19.

Li M, Gebremedhin K, Ma D, Pu Z, Xiong T, Xu Y . Conditionally Activatable Photoredox Catalysis in Living Systems. J Am Chem Soc. 2021; 144(1):163-173. DOI: 10.1021/jacs.1c07372. View

20.

Tsujii M, Kawano S, DuBois R . Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci U S A. 1997; 94(7):3336-40. PMC: 20370. DOI: 10.1073/pnas.94.7.3336. View