A Comparative Study of Photobiological and Photophysical Characteristic of Meso-Tetraphenylporphyrin and Meso-Tetraphenylchlorin as Photosensitizers for Photodynamic Therapy
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Keywords:
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Meso-Tetraphenylporphyrin, Meso-Tetraphenylchlorin, Photodynamic Therapy, Photosensitizer, Photophysical Properties, Photobiological Properties
Abstract
Photosensitizer modifications are needed to improve the performance of Photodynamic Therapy (PDT) for the treatment of cancer. This work appraised the photophysical and photobiological characteristics of tetrapyrrolic macrocycles. Meso-tetraphenylporphyrin (m-TPP) and meso-tetraphenylchlorin (m-TPC) represent non-reduced and reduced pyrrole rings tetrapyrrolic macrocycles, respectively. The absorption spectra of m-TPP and m-TPC were performed. The relative quantum yield of singlet oxygen (ΦΔ) was measured at two different pH (6.3 and 7.4) relative to chlorine e6. Dark toxicity was monitored using the MTT assay on breast cancer T47D and NIH 3T3 cell lines. In addition, the stability of the compounds under indirect sunlight was also observed. The absorption maxima of the Q1 band of both compounds are at a longer wavelength. The Q1 peak of a reduced pyrrole ring is more intense than the non-reduced pyrrole ring with the lowest energy transition undergoing a redshift. The singlet oxygen generations are higher at pH 7.4 for both compounds with them-TPC showed a higher relative singlet oxygen quantum yield. In addition, the photosensitizers are stable under indirect sunlight radiation. m-TPC has higher cellular uptake than m-TPP in both cell lines. The dark toxicity of m-TPC is higher than m-TPP in T47D cells. However, the opposite occurred in observing dark toxicity in the NIH 3T3 cell line. Our study concludes that the cellular uptake and ΦΔ can be enhanced by reducing the pyrrole ring of the tetrapyrrole macrocycle. Therefore, m-TPC proved to be a better photosensitizer than m-TPP.
References
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Mojzisova, H., Bonneau, S., Brault, D. (2007). Structural and Physico-Chemical Determinants of the Interactions of Macrocyclic Photosensitizers with Cells. European Biophysics Journal : EBJ, 36(8), 943–953. DOI: 10.1007/s00249-007-0204-9.
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Parkhats, M., Galievsky, V., Stashevsky, A., Trukhacheva, T., Dzhagarov, B. (2009). Dynamics and Efficiency of the Photosensitized Singlet Oxygen Formation by Chlorin e6: the Effects of the Solution pH and Polyvinylpyrrolidone. Optics and Spectroscopy, 107, 974–980. DOI: 10.1134/S0030400X09120200.
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Reddi, E. (1997). Role of Delivery Vehicles for Photosensitizers in the Photodynamic Therapy of Tumours. Journal of Photochemistry and Photobiology B, Biology, 37(3), 189–195. DOI: 10.1016/s1011-1344(96)07404-0.
Roeder, B., Naether, D., Lewald, T., Braune, M., Nowak, C., Freyer, W. (1990). Photophysical Properties and Photodynamic Activity in Vivo of Some Tetrapyrroles. Biophysical Chemistry, 35(2–3), 303–312. DOI: 10.1016/0301-4622(90)80017-2.
Spiller, W., Kliesch, H., Wöhrle, D., Hackbarth, S., Röder, B., Schnurpfeil, G. (1998). Singlet Oxygen Quantum Yields of Different Photosensitizers in Polar Solvents and Micellar Solutions. Journal of Porphyrins and Phthalocyanines, 02(02), 145–158. DOI: 10.1002/(SICI)1099-1409(199803/04)2:2<145::AID-JPP60>3.0.CO;2-2.
8.
Baskaran, R., Lee, J., Yang, S.-G. (2018). Clinical Development of Photodynamic Agents and Therapeutic Applications. Biomaterials Research, 22, 25. DOI: 10.1186/s40824-018-0140-z.
Bonnett, R. (1995). Photosensitizers of the Porphyrin and Phthalocyanine Series for Photodynamic Therapy. Chemical Society Reviews, 24(1), 19–33. DOI: 10.1039/CS9952400019.
Bose, B., Dube, A. (2008). Photodynamic Efficacy of Chlorin p6: a pH-Dependent Study in Aqueous and Lipid Environment. Journal of Photochemistry and Photobiology B, Biology, 93(1), 32–35. DOI: 10.1016/j.jphotobiol.2008.06.007.
Canete, M., Villanueva, A., Dominguez, V., Polo, S., Juarranz, A., Stockert, J.C. (1998). Meso-Tetraphenylporphyrin: Photosensitizing Properties and Cytotoxic Effects on Cultured Tumor Cells. International Journal of Oncology, 13(3), 497–504. DOI: 10.3892/ijo.13.3.497.
Chen, Y., Sajjad, M., Wang, Y., Batt, C., Nabi, H.A., Pandey, R.K. (2011). TSPO 18 kDa (PBR) Targeted Photosensitizers for Cancer Imaging (PET) and PDT. ACS Medicinal Chemistry Letters, 2(2), 136–141. DOI: 10.1021/ml100211g.
Djalil, A.D., Kartasasmita, R.A., Ibrahim, S. Tjahjono, D. (2012). Toxicity Prediction of Photosensitizers Bearing Carboxylic Acid Groups by ECOSAR and Toxtree. Journal of Pharmacology and Toxicology, 7(5), 219–230. DOI: 0.3923/jpt.2012.219.230.
Djalil, A.D., Fadhilah, N., Saputri, D., Hamad, A. (2016). Hubungan Kuantitatif Struktur-Aktifitas dan Doking Molekular Senyawa Meso- Tetraphenylporphyrin dan Meso-Tetraphenylchlorin. 3(1), 19–31. DOI: 10.20527/jps.v3i1.5831.
Djalil, A.D., Nurulita, N.A., Limantara, L.W., Ibrahim, S., Tjahjono, D.H. (2012). Biological Evaluations of Protoporphyrin IX, Pheophorbide a, and Its 1-Hydroxyethyl Derivatives for Application in Photodynamic Therapy. International Journal of Pharmacy and Pharmaceutical Sciences, 4(3), 741–746.
Dougherty, T.J., Gomer, C.J., Henderson, B.W., Jori, G., Kessel, D., Korbelik, M., Moan, J., Peng, Q. (1998). Photodynamic Therapy. Journal of the National Cancer Institute, 90(12), 889–905. DOI: 10.1093/jnci/90.12.889.
Foroozandeh, P., Aziz, A.A. (2018). Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles. Nanoscale Research Letters, 13(1), 339. DOI: 10.1186/s11671-018-2728-6.
Fukuhara, H., Yamamoto, S., Karashima, T., Inoue, K. (2021). Photodynamic Diagnosis and Therapy for Urothelial Carcinoma and Prostate Cancer: New Imaging Technology and Therapy. International Journal of Clinical Oncology, 26(1), 18–25. DOI: 10.1007/s10147-020-01704-y.
Gunaydin, G., Gedik, M.E., Ayan, S. (2021). Photodynamic Therapy For the Treatment and Diagnosis of Cancer–a Review of the Current Clinical Status. In Frontiers in Chemistry Volume 9. DOI: 10.3389/fchem.2021.686303.
Jezek, P., Nekvasil, M., Skobisová, E., Urbánková, E., Jirsa, M., Zadinová, M., Poucková, P., Klepácek, I. (2003). Experimental Photodynamic Therapy with MESO-Tetrakisphenylporphyrin (TPP) in Liposomes Leads to Disintegration of Human Amelanotic Melanoma Implanted to Nude Mice. International Journal of Cancer, 103(5), 693–702. DOI: 10.1002/ijc.10857.
Kim, H.-I., Wilson, B.C. (2020). Photodynamic Diagnosis and Therapy for Peritoneal Carcinomatosis from Gastrointestinal Cancers: Status, Opportunities, and Challenges. Journal of Gastric Cancer, 20(4), 355–375. DOI: 10.5230/jgc.2020.20.e39.
Kraljić, I., Mohsni, S.E. (1978). A New Method for the Detection of Singlet Oxygen in Aqueous Solutions. Photochemistry and Photobiology, 28(4–5), 577–581. DOI: 10.1111/j.1751-1097.1978.tb06972.x.
Krumova, K., Cosa, G. (2016). Chapter 1 Overview of Reactive Oxygen Species. In Singlet Oxygen: Applications in Biosciences and Nanosciences Volume 1. The Royal Society of Chemistry. DOI: 10.1039/9781782622208-00001.
Lovcinský, M., Borecký, J., Kubát, P., Jezek, P. (1999). Meso-Tetraphenylporphyrin in Liposomes as a Suitable Photosensitizer for Photodynamic Therapy of Tumors. General Physiology and Biophysics, 18(2), 107–118. PMID: 10517287.
Mojzisova, H., Bonneau, S., Brault, D. (2007). Structural and Physico-Chemical Determinants of the Interactions of Macrocyclic Photosensitizers with Cells. European Biophysics Journal : EBJ, 36(8), 943–953. DOI: 10.1007/s00249-007-0204-9.
Osaki, T., Takagi, S., Hoshino, Y., Okumura, M., Fujinaga, T. (2006). Intracellular Localization and Concentration as Well as Photodynamic Effects of Benzoporphyrin Derivative Monoacid Ring A in Four Types of Rodent Tumor Cells. Cancer Letters, 243(2), 281–292. DOI: 10.1016/j.canlet.2005.11.044.
Owari, T., Iwamoto, T., Anai, S., Miyake, M., Nakai, Y., Hori, S., Hara, T., Ishii, T., Ota, U., Torimoto, K., Kuniyasu, H., Fujii, T., Tanaka, N., Fujimoto, K. (2021). The Sustaining of Fluorescence in Photodynamic Diagnosis After the Administration of 5-Aminolevulinic Acid in Carcinogen-Induced Bladder Cancer Orthotopic Rat Model and Urothelial Cancer Cell Lines. Photodiagnosis and Photodynamic Therapy, 34, 102309. DOI: 10.1016/j.pdpdt.2021.102309.
Parkhats, M., Galievsky, V., Stashevsky, A., Trukhacheva, T., Dzhagarov, B. (2009). Dynamics and Efficiency of the Photosensitized Singlet Oxygen Formation by Chlorin e6: the Effects of the Solution pH and Polyvinylpyrrolidone. Optics and Spectroscopy, 107, 974–980. DOI: 10.1134/S0030400X09120200.
Radunz, S., Wedepohl, S., Röhr, M., Calderón, M., Tschiche, H.R., Resch-Genger, U. (2020). pH-Activatable Singlet Oxygen-Generating Boron-dipyrromethenes (BODIPYs) for Photodynamic Therapy and Bioimaging. Journal of Medicinal Chemistry, 63(4), 1699–1708. DOI: 10.1021/acs.jmedchem.9b01873.
Reddi, E. (1997). Role of Delivery Vehicles for Photosensitizers in the Photodynamic Therapy of Tumours. Journal of Photochemistry and Photobiology B, Biology, 37(3), 189–195. DOI: 10.1016/s1011-1344(96)07404-0.
Roeder, B., Naether, D., Lewald, T., Braune, M., Nowak, C., Freyer, W. (1990). Photophysical Properties and Photodynamic Activity in Vivo of Some Tetrapyrroles. Biophysical Chemistry, 35(2–3), 303–312. DOI: 10.1016/0301-4622(90)80017-2.
Spiller, W., Kliesch, H., Wöhrle, D., Hackbarth, S., Röder, B., Schnurpfeil, G. (1998). Singlet Oxygen Quantum Yields of Different Photosensitizers in Polar Solvents and Micellar Solutions. Journal of Porphyrins and Phthalocyanines, 02(02), 145–158. DOI: 10.1002/(SICI)1099-1409(199803/04)2:2<145::AID-JPP60>3.0.CO;2-2.
8.
Authors
Djalil, A. D., Susanti, Erlita, F. M. ., Mustafa, A. F., Hamad, A. ., & Suwandri. (2022). A Comparative Study of Photobiological and Photophysical Characteristic of Meso-Tetraphenylporphyrin and Meso-Tetraphenylchlorin as Photosensitizers for Photodynamic Therapy. Science and Technology Indonesia, 7(2), 213–219. https://doi.org/10.26554/sti.2022.7.2.213-219
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