Photosensitizing Herbs as Potential Therapeutics: A Prospective Insights into their Mechanisms for the Development of Novel Drug Leads in War with Cancer and Other Human Diseases

Mohamed Ali Seyed; Elodemi Mahmoud

doi:10.3889/oamjms.2024.11883

Authors

Mohamed Ali Seyed Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Kingdom of Saudi Arabia https://orcid.org/0000-0003-4469-1221
Elodemi Mahmoud Department of Pharmacology, Faculty of Medicine, University of Tabuk, Tabuk, Kingdom of Saudi Arabia

DOI:

https://doi.org/10.3889/oamjms.2024.11883

Keywords:

Photosensitizing agents, Hypocrellins, Hypericin, Anti-tumor, Curcumin, PDT

Abstract

In recent years, photodynamic therapy (PDT) has been accepted as an alternative option for the treatment of a wide spectrum of human ailments. It is a minimally invasive treatment that involves the interaction of a non-toxic photosensitizer. In PDT, combining photosensitizing (PS) agent that absorbs specified wavelength of light, which in turn produces free radical molecules to eliminate unwanted cells and tissues. The photosensitization process is activated by the light-induced excitation of molecules within the tissue. Bioactive principles acquired from plants documented as nature-inspired potential photosensitizers with varied properties against microbes, insects, or tumor cells. PDT is a promising method for removing diverse types of cancers but needs to be recognized in therapy as conventional chemotherapy. At present, natural compounds with PS properties are being continuously unearthed and identified. As of now, hundreds of photosensitive drugs or drug leads identified from natural sources with reduced or no toxicity to healthy tissues and no side effects encourage investigators to pursue natural PS for PDT. Although existing PS was developed years back, only a handful of them are engaged in human clinical applications. The main classes of natural photosensitizers discussed in this review are chlorophylls (hypocrellin A and B), hypericin, chlorins (Chlorin e6), and other emerging ones such as curcumin. Hence, the present review aimed to explore the efficacious PS properties of a few herbal-derived PS, preferably the potential ones in terms of specificity, and mechanism of action, inducing less or no toxicity to normal cells but their other medicinal applications.

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References

Beutler JA. Natural products as a foundation for drug discovery. Curr Protoc Pharmacol. 2009;46:9.11.1-9.21. https://doi.org/10.1002/0471141755.ph0911s46 PMid:20161632 DOI: https://doi.org/10.1002/0471141755.ph0911s46

Nasim N, Sandeep IS, Mohanty S. Plant-derived natural products for drug discovery: Current approaches and prospects. Nucleus (Calcutta). 2022;65(3):399-411. https://doi.org/10.1007/s13237-022-00405-3 PMid:36276225 DOI: https://doi.org/10.1007/s13237-022-00405-3

Bohr A, Memarzadeh K. The rise of artificial intelligence in healthcare applications. In: Artificial Intelligence in Healthcare. Cambridge: Academic Press; 2020. p. 25-60. DOI: https://doi.org/10.1016/B978-0-12-818438-7.00002-2

Mathur S, Hoskins C. Drug development: Lessons from nature. Biomed Rep. 2017;6(6):612-4. https://doi.org/10.3892/br.2017.909 PMid:28584631 DOI: https://doi.org/10.3892/br.2017.909

Mello MM. Barriers to ensuring access to affordable prescription drugs. Annu Rev Pharmacol Toxicol. 2020;60:275-89. https://doi.org/10.1146/annurev-pharmtox-010919-023518 PMid:31136248 DOI: https://doi.org/10.1146/annurev-pharmtox-010919-023518

Ali SM, Chee SK, Yuen GY, Olivo M. Photodynamic therapy induced Fas-mediated apoptosis in human carcinoma cells. Int J Mol Med 2002;9(3):257-70. DOI: https://doi.org/10.3892/ijmm.9.3.257

Diwu Z. Novel therapeutic and diagnostic applications of hypocrellins and hypericins. Photochem Photobiol. 1995;61(6):529-39. https://doi.org/10.1111/j.1751-1097.1995.tb09903.x PMid:7568399 DOI: https://doi.org/10.1111/j.1751-1097.1995.tb09903.x

Diwu ZJ, Haugland RP, Liu J, Lown JW, Miller GG, Moore RB, et al. Photosensitization by anticancer agents 21: New perylene- and

aminonaphthoquinones. Free Radic Biol Med. 1996;20(4):589- 93. https://doi.org/10.1016/0891-5849(95)02061-6 PMid:8904300 DOI: https://doi.org/10.1016/0891-5849(95)02061-6

Xu S, Chen S, Zhang M, Shen T, Zhao Y, Liu Z, et al. Butylamino-demethoxy-hypocrellins and photodynamic therapy decreases human cancer in vitro and in vivo. Biochim Biophys Acta. 2001;1537(3):222-32. https://doi.org/10.1016/s0925-4439(01)00074-6 PMid:11731224 DOI: https://doi.org/10.1016/S0925-4439(01)00074-6

Wainwright CL, Teixeira MM, Adelson DL, Braga FC, Buenz EJ, David B, et al. Future directions for the discovery of natural product-derived immunomodulating drugs: An IUPHAR positional review. Pharmacol Res. 2022;177:106076. https://doi.org/10.1016/j.phrs.2022.106076 PMid:35074524 DOI: https://doi.org/10.1016/j.phrs.2022.106207

Veeresham C. Natural products derived from plants as a source of drugs. J Adv Pharm Technol Res. 2012;3(4):200-1. https://doi.org/10.4103/2231-4040.104709 PMid:23378939 DOI: https://doi.org/10.4103/2231-4040.104709

Talib WH, Alsalahat I, Daoud S, Abutayeh RF, Mahmod AI. Plant-derived natural products in cancer research: Extraction, mechanism of action, and drug formulation. Molecules. 2020;25(22):10.3390/molecules25225319. https://doi.org/10.3390/molecules25225319 PMid:33202681 DOI: https://doi.org/10.3390/molecules25225319

Atanasov AG, Zotchev SB, Dirsch VM, International Natural Product Sciences Taskforce, Supuran CT. Natural products in drug discovery: Advances and opportunities. Nat Rev Drug Discov. 2021;20(3):200-16. https://doi.org/10.1038/s41573-020-00114-z PMid:33510482 DOI: https://doi.org/10.1038/s41573-020-00114-z

Wagner H, Ulrich-MG. Synergy research: Approaching a new generation of phytopharmaceuticals. Phytomedicine. 2009;16(2- 3):97-110. https://doi.org/10.1016/j.phymed.2008.12.018 PMid:19211237 DOI: https://doi.org/10.1016/j.phymed.2008.12.018

Geysen HM, Schoenen F, Wagner D, Wagner R. Combinatorial compound libraries for drug discovery: An ongoing challenge. Nat Rev Drug Discov. 2003;2(3):222-30. https://doi.org/10.1038/nrd1035 PMid:12612648 DOI: https://doi.org/10.1038/nrd1035

Vijayaraghavan K, Rajkumar J, Bukhari SN, Al-Sayed B, Seyed MA. Chromolaena odorata: A neglected weed with a wide spectrum of pharmacological activities (Review). Mol Med Rep. 2017;15(3):1007-16. https://doi.org/10.3892/mmr.2017.6133 PMid:28112383 DOI: https://doi.org/10.3892/mmr.2017.6133

Jantan I, Syed Nasir AB, Mohamed Ali SM, Wai LK, Mesaik MA. The evolving role of natural products from the tropical rainforests as a replenishable source of new drug leads. In: Drug Discovery and Development-From Molecules to Medicine. London: IntechOpen; 2015. p. 3-38. DOI: https://doi.org/10.5772/59603

Amit KA, Chandrashekar DR, Shripal MC. Natural Products in Drug Discovery. Pharmacognosy - Medicinal Plants. London: IntechOpen; 2019.

Seyed MA, Vijayaraghavan K. Dengue virus infections and anti- dengue virus activities of Andrographis paniculata. Asian Pac J Trop Med. 2020;13(2):49. DOI: https://doi.org/10.4103/1995-7645.275412

Katiyar C, Gupta A, Kanjilal S, Katiyar S. Drug discovery from plant sources: An integrated approach. Ayu. 2012;33(1):10-9. https://doi.org/10.4103/0974-8520.100295 PMid:23049178 DOI: https://doi.org/10.4103/0974-8520.100295

Seyed MA. A comprehensive review on Phyllanthus derived natural products as potential chemotherapeutic and immunomodulators for a wide range of human diseases. Biocat Agric Biotechnol. 2019;17:529-37. DOI: https://doi.org/10.1016/j.bcab.2019.01.008

Li CQ, Lei HM, Hu QY, Li GH, Zhao PJ. Recent advances in the synthetic biology of natural drugs. Front Bioeng Biotechnol. 2021;9:691152. https://doi.org/10.3389/fbioe.2021.691152 PMid:34395399 DOI: https://doi.org/10.3389/fbioe.2021.691152

Mouhssen L. The success of natural products in drug discovery. Pharmacol Pharm. 2013;4:17-31. DOI: https://doi.org/10.4236/pp.2013.43A003

Dougherty TJ. Photodynamic therapy. Photochem Photobiol. 1993;58:895-900. DOI: https://doi.org/10.1111/j.1751-1097.1993.tb04990.x

Ali SM, Olivo M, Yuen GY, Chee SK. Photodynamic-induced apoptosis of human nasopharyngeal carcinoma cells using Hypocrellins. Int J Oncol. 2001;19(3):633-43. https://doi.org/10.3892/ijo.19.3.633 PMid:11494047 DOI: https://doi.org/10.3892/ijo.19.3.633

Ali SM, Olivo M. Bio-distribution and subcellular localization of Hypericin and its role in PDT induced apoptosis in cancer cells. Int J Oncol. 2002;21(3):531-40. DOI: https://doi.org/10.3892/ijo.21.3.531

Robertson CA, Evans DH, Abrahamse H. Photodynamic therapy (PDT): A short review on cellular mechanisms and cancer research applications for PDT. J Photochem Photobiol B. 2009;96(1):1-8. https://doi.org/10.1016/j.jphotobiol.2009.04.001 PMid:19406659 DOI: https://doi.org/10.1016/j.jphotobiol.2009.04.001

Aziz B, Aziz I, Khurshid A, Raoufi E, Esfahani FN, Jalilian Z, et al. An overview of potential natural photosensitizers in cancer photodynamic therapy. Biomedicines. 2023;11(1):224. https://doi.org/10.3390/biomedicines11010224 PMid:36672732 DOI: https://doi.org/10.3390/biomedicines11010224

Hamblin MR, Hasan T. Photodynamic therapy: A new antimicrobial approach to infectious disease? Photochem Photobiol Sci. 2004;3(5):436-50. https://doi.org/10.1039/ b311900a PMid:15122361 DOI: https://doi.org/10.1039/b311900a

Gitika BK, Sharma SK, Huang YY, Dai T, Hamblin MR. Photodynamic therapy for infections. Lasers Surg Med. 2011;43(7):755-67. https://doi.org/10.1002/lsm.21080 PMid:22057503 DOI: https://doi.org/10.1002/lsm.21080

Sharma SK, Mroz P, Dai T, Huang YY, St Denis TG, Hamblin MR. Photodynamic therapy for cancer and for infections: What is the difference? Isr J Chem. 2012;52(8-9):691-705. https://doi.org/10.1002/ijch.201100062 PMid:23248387 DOI: https://doi.org/10.1002/ijch.201100062

Ali-Seyed M, Bhuvaneswari R, Soo KC, Olivo M. Photolon™ --photosensitization induces apoptosis via ROS- mediated cross-talk between mitochondria and lysosomes. Int J Oncol. 2011;39(4):821-31. https://doi.org/10.3892/ijo.2011.1109 PMid:21725591 DOI: https://doi.org/10.3892/ijo.2011.1109

Geltzer A, Turalba A, Vedula SS. Surgical implantation of steroids with antiangiogenic characteristics for treating neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2013;1(1):CD005022. https://doi.org/10.1002/14651858. CD005022.pub3 PMid:23440797 DOI: https://doi.org/10.1002/14651858.CD005022.pub3

Buytaert E, Dewaele M, Agostinis P. Molecular effectors of multiple cell death pathways initiated by photodynamic therapy. Biochim Biophys Acta. 2007;1776(1):86-107. https://doi. org/10.1016/j.bbcan.2007.07.001 PMid:17693025 DOI: https://doi.org/10.1016/j.bbcan.2007.07.001

Luo Y, Kessel D. Initiation of apoptosis versus necrosis by photodynamic therapy with chloroaluminum phthalocyanine (Review). Photochem Photobiol. 1997;66(4):479-83. https://doi.org/10.1111/j.1751-1097.1997.tb03176.x PMid:9337618 DOI: https://doi.org/10.1111/j.1751-1097.1997.tb03176.x

Piette J, Volanti C, Vantieghem A, Matroule JY, Habraken Y, Agostinis P. Cell death and growth arrest in response to photodynamic therapy with membrane-bound photosensitizers. Biochem Pharmacol. 2003;66(8):1651-9. https://doi.org/10.1016/s0006-2952(03)00539-2 PMid:14555246 DOI: https://doi.org/10.1016/S0006-2952(03)00539-2

Wang KN, Liu LY, Qi G, Chao XJ, Ma W, Yu Z, et al. Light-driven cascade mitochondria-to-nucleus photosensitization in cancer cell ablation. Adv Sci (Weinh). 2021;8(8):2004379. https://doi.org/10.1002/advs.202004379 PMid:33898198 DOI: https://doi.org/10.1002/advs.202004379

Yoo JO, Ha KS. New insights into the mechanisms for photodynamic therapy-induced cancer cell death. Int Rev Cell Mol Biol. 2012;295:139-74. https://doi.org/10.1016/ B978-0-12-394306-4.00010-1 PMid:22449489

Yang J, Griffin A, Qiang Z, Ren J. Organelle-targeted therapies: A comprehensive review on system design for enabling precision oncology. Signal Transduct Target Ther. 2022;7(1):379. https://doi.org/10.1038/s41392-022-01243-0 PMid:36402753 DOI: https://doi.org/10.1038/s41392-022-01243-0

Nowak-Stępniowska A, Wiktorska K, Małecki M, Romiszewska A, Padzik-Graczyk A. Cytotoxicity of PP(Arg) (2)- and Hp(Arg)(2)-mediated photodynamic therapy and early stage of apoptosis induction in prostate carcinoma in vitro. Acta Biochim Pol. 2011;58(4):497-505. DOI: https://doi.org/10.18388/abp.2011_2216

Lima E, Reis LV. Photodynamic therapy: From the basics to the current progress of N-heterocyclic-bearing dyes as effective photosensitizers. Molecules. 2023;28(13):5092. https://doi.org/10.3390/molecules28135092 PMid:37446758 DOI: https://doi.org/10.3390/molecules28135092

Marrelli M, Menichini G, Provenzano E, Conforti F. Applications of natural compounds in the photodynamic therapy of skin cancer. Curr Med Chem. 2014;21(12):1371-90. https://doi.org/10.2174/092986732112140319094324 PMid:23531223 DOI: https://doi.org/10.2174/092986732112140319094324

Vaou N, Stavropoulou E, Voidarou C, Tsigalou C, Bezirtzoglou E. Towards advances in medicinal plant antimicrobial activity: A review study on challenges and future perspectives. Microorganisms. 2021;9(10):2041. https://doi.org/10.3390/microorganisms9102041 PMid:34683362 DOI: https://doi.org/10.3390/microorganisms9102041

Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod. 2016;79(3):629-61. https://doi.org/10.1021/acs.jnatprod.5b01055 PMid:26852623 DOI: https://doi.org/10.1021/acs.jnatprod.5b01055

Juarranz A, Jaén P, Sanz-Rodríguez F, Cuevas J, González S. Photodynamic therapy of cancer. Basic principles and applications. Clin Transl Oncol. 2008;10(3):148-54. https://doi.org/10.1007/s12094-008-0172-2 PMid:18321817 DOI: https://doi.org/10.1007/s12094-008-0172-2

O’Connor AE, Gallagher WM, Byrne AT. Porphyrin and nonporphyrin photosensitizers in oncology: Preclinical and clinical advances in photodynamic therapy. Photochem Photobiol. 2009;85(5):1053-74. https://doi. org/10.1111/j.1751-1097.2009.00585.x PMid:19682322 DOI: https://doi.org/10.1111/j.1751-1097.2009.00585.x

Hamblin MR, Chiang LY, Lakshmanan S, Huang YY, Garcia- Diaz M, Karimi M, et al. Nanotechnology for photodynamic therapy: A perspective from the Laboratory of Dr. Michael R. Hamblin in the Wellman Center for Photomedicine at Massachusetts General Hospital and Harvard Medical School. Nanotechnol Rev. 2015;4(4):359-72. https://doi.org/10.1515/ntrev-2015-0027 PMid: 26640747 DOI: https://doi.org/10.1515/ntrev-2015-0027

Pervaiz S, Olivo M. Art and science of photodynamic therapy. Clin Exp Pharmacol Physiol. 2006;33(5-6):551-6. https://doi.org/10.1111/j.1440-1681.2006.04406.x PMid:16700893 DOI: https://doi.org/10.1111/j.1440-1681.2006.04406.x

Algorri JF, López-Higuera JM, Rodríguez-Cobo L, Cobo A. Advanced light source technologies for photodynamic therapy of skin cancer lesions. Pharmaceutics. 2023;15(8):2075. https://doi.org/10.3390/pharmaceutics15082075 PMid:37631289 DOI: https://doi.org/10.3390/pharmaceutics15082075

Kubrak TP, Kołodziej P, Sawicki J, Mazur A, Koziorowska K, Aebisher D. Some natural photosensitizers and their medicinal properties for use in photodynamic therapy. Molecules. 2022;27(4):1192. https://doi.org/10.3390/molecules27041192 PMid:35208984 DOI: https://doi.org/10.3390/molecules27041192

Brancaleon L, Moseley H. Laser and non-laser light sources for photodynamic therapy. Lasers Med Sci. 2002;17(3):173-86. https://doi.org/10.1007/s101030200027 PMid:12181632 DOI: https://doi.org/10.1007/s101030200027

Boyle RW, Dolphin D. Structure and biodistribution relationships of photodynamic sensitizers. Photochem Photobiol. 1996;64(3):469-85. https://doi.org/10.1111/j.1751-1097.1996.tb03093.x PMid:8806226 DOI: https://doi.org/10.1111/j.1751-1097.1996.tb03093.x

Benov L. Photodynamic therapy: Current status and future directions. Med Princ Pract. 2015;24 Suppl 1(Suppl 1):14-28. https://doi.org/10.1159/000362416 PMid:24820409 DOI: https://doi.org/10.1159/000362416

Detty MR, Gibson SL, Wagner SJ. Current clinical and preclinical photosensitizers for use in photodynamic therapy. J Med Chem. 2004;47(16):3897-915. https://doi.org/10.1021/jm040074b PMid:15267226 DOI: https://doi.org/10.1021/jm040074b

Udrea AM, Smarandache A, Dinache A, Mares C, Nistorescu S, Avram S, et al. Photosensitizers-loaded nanocarriers for enhancement of photodynamic therapy in melanoma treatment. Pharmaceutics. 2023;15(8):2124. https://doi.org/10.3390/pharmaceutics15082124 PMid:37631339 DOI: https://doi.org/10.3390/pharmaceutics15082124

Palumbo G. Photodynamic therapy and cancer: A brief sightseeing tour. Expert Opin Drug Deliv. 2007;4(2):131-48. https://doi.org/10.1517/17425247.4.2.131 PMid:17335411 DOI: https://doi.org/10.1517/17425247.4.2.131

Sarbadhikary P, George BP, Abrahamse H. Potential application of photosensitizers with high-Z elements for synergic cancer therapy. Front Pharmacol. 2022;13:921729. https://doi.org/10.3389/fphar.2022.921729 PMid:35837287 DOI: https://doi.org/10.3389/fphar.2022.921729

Downum KR, Wen J. The Occurrence of Photosensitizers among higher plants. In: Light-Activated Pest Control. Ch.

Washington, DC: The American Chemical Society; 1995. p. 135-43.

Thirumurugan D, Cholarajan A, Raja SS, Vijayakumar R. An introductory chapter. In: Secondary Metabolites-Sources Applications. London: IntechOpen; 2018. p. 1-21. DOI: https://doi.org/10.5772/intechopen.79766

Kennedy DO, Wightman EL. Herbal extracts and phytochemicals: Plant secondary metabolites and the enhancement of human brain function. Adv Nutr. 2011;2(1):32-50. https://doi.org/10.3945/an.110.000117 PMid:22211188 DOI: https://doi.org/10.3945/an.110.000117

Marrelli M, Statti G, Conforti F. A Review of Biologically Active Natural Products from Mediterranean Wild Edible Plants: Benefits in the Treatment of Obesity and Its Related Disorders. Molecules. 2020;25(3):649. https://doi.org/10.3390/molecules25030649 PMidD: 32028716 DOI: https://doi.org/10.3390/molecules25030649

Jong WW, Tan PJ, Kamarulzaman FA, Mejin M, Lim D, Ang I, et al. Photodynamic activity of plant extracts from Sarawak, Borneo. Chem Biodivers. 2013;10(8):1475-86. https://doi.org/10.1002/cbdv.201200303 PMid:23939795 DOI: https://doi.org/10.1002/cbdv.201200303

Mansoori B, Mohammadi A, Amin Doustvandi M, Mohammadnejad F, Kamari F, Gjerstorff MF, et al. Photodynamic therapy for cancer: Role of natural products. Photodiagnosis Photodyn Ther. 2019;26:395-404. https://doi.org/10.1016/j.pdpdt.2019.04.033 PMid:31063860 DOI: https://doi.org/10.1016/j.pdpdt.2019.04.033

Foresto E, Gilardi P, Ibarra LE, Cogno IS. Light-activated green drugs: How we can use them in photodynamic therapy and mass-produce them with biotechnological tools. Phytomed Plus. 2021;1(3):100044. https://doi.org/10.1016/j.phyplu.2021.100044 DOI: https://doi.org/10.1016/j.phyplu.2021.100044

haneshwar S, Patil K, Bulbule M, Kinjawadekar V, Joshi D, Joshi V. Photodynamic therapy for cancer. Int J Pharm Sci Rev Res. 2014;27(2):125-41.

Baskaran R, Lee J, Yang SG. Clinical development of photodynamic agents and therapeutic applications. Biomater Res. 2018;22:25. https://doi.org/10.1186/s40824-018-0140-z PMid:30275968 DOI: https://doi.org/10.1186/s40824-018-0140-z

Berlanda J, Kiesslich T, Engelhardt V, Krammer B, Plaetzer K. Comparative in vitro study on the characteristics of different photosensitizers employed in PDT. J Photochem Photobiol B. 2010;100(3):173-80. https://doi.org/10.1016/j.jphotobiol.2010.06.004 PMid:20599390 DOI: https://doi.org/10.1016/j.jphotobiol.2010.06.004

Almadi KH, Alkahtany MF, Almutairi B. Influence of synthetic and natural photosensitizers activated by photodynamic therapy on extrusion bond strength of fiber post to radicular dentin. Pak J Med Sci. 2021;37(7):1912-7. https://doi.org/10.12669/pjms.37.7.4331 PMid:34912417 DOI: https://doi.org/10.12669/pjms.37.7.4331

Shrestha R, Mallik SK, Lim J, Gurung P, Magar TBT, Kim YW. Efficient synthesis of chlorin e6 and its potential photodynamic immunotherapy in mouse melanoma by the abscopal effect. Int J Mol Sci. 2023;24(4):10.3390/ijms24043901. https://doi.org/10.3390/ijms24043901 PMid:36835310 DOI: https://doi.org/10.3390/ijms24043901

Sobaniec S, Bernaczyk P, Pietruski J, Cholewa M, Skurska A, Dolińska E, et al. Clinical assessment of the efficacy of photodynamic therapy in the treatment of oral lichen planus. Lasers Med Sci. 2013;28(1):311-6. https://doi.org/10.1007/s10103-012-1153-9 PMid:22814895 DOI: https://doi.org/10.1007/s10103-012-1153-9

Allison RR, Sibata C, Mang TS, Bagnato VS, Downie GH, Hu XH, et al. Photodynamic therapy for chest wall recurrence from breast cancer. Photodiagnosis Photodyn Ther. 2004;1(2):157- 71. https://doi.org/10.1016/S1572-1000(04)00039-0 PMid:25048186 DOI: https://doi.org/10.1016/S1572-1000(04)00039-0

Overchuk M, Weersink RA, Wilson BC, Zheng G. Photodynamic and photothermal therapies: Synergy opportunities for nanomedicine. ACS Nano. 2023;17(9):7979-8003. https://doi.org/10.1021/acsnano.3c00891 PMid:37129253 DOI: https://doi.org/10.1021/acsnano.3c00891

Kessel D, Luo Y. Mitochondrial photodamage and PDT-induced apoptosis. J Photochem Photobiol B. 1998;42(2):89-95. https://doi.org/10.1016/s1011-1344(97)00127-9 PMid:9540214 DOI: https://doi.org/10.1016/S1011-1344(97)00127-9

Galanou MC, Theodossiou TA, Tsiourvas D, Sideratou Z, Paleos CM. Interactive transport, subcellular relocation and enhanced phototoxicity of hypericin encapsulated in guanidinylated liposomes via molecular recognition. Photochem Photobiol. 2008;84(5):1073-83. https://doi.org/10.1111/j.1751-1097.2008.00392.x PMid:18627515 DOI: https://doi.org/10.1111/j.1751-1097.2008.00392.x

Zhao J, Wu W, Sun J, Guo S. Triplet photosensitizers: From molecular design to applications. Chem Soc Rev. 2013;42(12):5323-51. https://doi.org/10.1039/c3cs35531d PMid:23450221 DOI: https://doi.org/10.1039/c3cs35531d

Blum NT, Zhang Y, Qu J, Lin J, Huang P. Recent advances in self-exciting photodynamic therapy. Front Bioeng Biotechnol. 2020;8:594491. https://doi.org/10.3389/fbioe.2020.594491 PMid:33195164 DOI: https://doi.org/10.3389/fbioe.2020.594491

Yoon I, Li JZ, Shim YK. Advance in photosensitizers and light delivery for photodynamic therapy. Clin Endosc. 2013;46(1):7- 23. https://doi.org/10.5946/ce.2013.46.1.7 PMid:23423543 DOI: https://doi.org/10.5946/ce.2013.46.1.7

Chin WW, Heng PW, Bhuvaneswari R, Lau WK, Olivo M. The potential application of chlorin e6-polyvinylpyrrolidone formulation in photodynamic therapy. Photochem Photobiol Sci. 2006;5(11):1031-7. https://doi.org/10.1039/b605772a PMid:17077899 DOI: https://doi.org/10.1039/b605772a

Trukhachova T. Safety and Efficacy of Photosensitizer Photolon (Fotolon) in Photodynamic Therapy. In: Proceeding SPIE 11070, 17th International Photodynamic Association World Congress, 1107037; 2019. https://doi.org/10.1117/12.2528083 DOI: https://doi.org/10.1117/12.2528083

Waidelich R. Laser-induced lithotripsy and photodynamic therapy in urology: A short introduction to current laser applications. Med Laser Appl. 2010;25(1):14-9. DOI: https://doi.org/10.1016/j.mla.2009.11.003

Li JH, Chen ZQ, Huang Z, Zhan Q, Ren FB, Liu JY, et al. In vitro study of low intensity ultrasound combined with different doses of PDT: Effects on C6 glioma cells. Oncol Lett. 2013;5(2):702-6. https://doi.org/10.3892/ol.2012.1060 PMid:23420417 DOI: https://doi.org/10.3892/ol.2012.1060

Copley L, Pauline WV, Wirtz KW, Iqbal Parker M, Leaner VD. Photolon, a chlorin e6 derivative, triggers ROS production and light-dependent cell death via necrosis. Int J Biochem Cell Biol. 2008;40(2):227-35. https://doi.org/10.1016/j.biocel.2007.07.014 PMid:17822943 DOI: https://doi.org/10.1016/j.biocel.2007.07.014

Isakau HA, Parkhats MV, Knyukshto VN, Dzhagarov BM, Petrov EP, Petrov PT. Toward understanding the high PDT efficacy of chlorin e6-polyvinylpyrrolidone formulations: Photophysical and molecular aspects of photosensitizer-polymer interaction in vitro. J Photochem Photobiol B. 2008;92(3):165- 74. https://doi.org/10.1016/j.jphotobiol.2008.06.004 PMid:18656379 DOI: https://doi.org/10.1016/j.jphotobiol.2008.06.004

JuzenieneA, Thu Tam TT, Iani V, Moan J. 5-Methyltetrahydrofolate can be photodegraded by endogenous photosensitizers. Free Radic Biol Med. 2009;47(8):1199-204. https://doi.org/10.1016/j.freeradbiomed.2009.07.030 PMid:19647791 DOI: https://doi.org/10.1016/j.freeradbiomed.2009.07.030

Trukhachova TV, Shliakhtsin SV, Cerkovsky DA, Istomin YP. A novel finished formulation of the photosensitizer Photolon® for topical application. Evaluation of the efficacy in patients with basal-cell carcinoma of the skin. Photodiagn Photodyn Ther. 2011;8:200-1. DOI: https://doi.org/10.1016/j.pdpdt.2011.03.258

Sharma S, Bakal J, Oliver-Fernandez A, Blair J. Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in age-related macular degeneration: Results of an effectiveness study. Arch Ophthalmol. 2004;122(6):853-6. https://doi.org/10.1001/archopht.122.6.853 PMid:15197060 DOI: https://doi.org/10.1001/archopht.122.6.853

Horibe S, Nagai J, Yumoto R, Tawa R, Takano M. Accumulation and photodynamic activity of chlorin e6 in cisplatin-resistant human lung cancer cells. J Pharm Sci. 2011;100(7):3010-7. https://doi.org/10.1002/jps.22501 PMid:21274848 DOI: https://doi.org/10.1002/jps.22501

Spikes JD. Chlorins as photosensitizers in biology and medicine. J Photochem Photobiol B. 1990;6(3):259-74. https://doi.org/10.1016/1011-1344(90)85096-f PMid:2120404 DOI: https://doi.org/10.1016/1011-1344(90)85096-F

Ding HL, Wang XL, Wang HW, Huang Z. Successful treatment of refractory facial acne using repeat short-cycle ALA-PDT: Case study. Photodiagnosis Photodyn Ther. 2011;8(4):343-6. https://doi.org/10.1016/j.pdpdt.2011.07.003 PMid:22122923 DOI: https://doi.org/10.1016/j.pdpdt.2011.07.003

Cabrera H, Castro J, Grassi HC, Andrades ED, López-Rivera SA. The effect of photodynamic therapy on contiguous untreated tumor. Dermatol Surg. 2012;38(7 Pt 1):1097-9. https://doi.org/10.1111/j.1524-4725.2012.02400.x PMid:22471374 DOI: https://doi.org/10.1111/j.1524-4725.2012.02400.x

Thong PS, Olivo M, Kho KW, Bhuvaneswari R, Chin WW, Ong KW, et al. Immune response against angiosarcoma following lower fluence rate clinical photodynamic therapy. J Environ Pathol Toxicol Oncol. 2008;27(1):35-42. https://doi.org/10.1615/jenvironpatholtoxicoloncol.v27.i1.40 PMid:18551894 DOI: https://doi.org/10.1615/JEnvironPatholToxicolOncol.v27.i1.40

Marchal S, François A, Dumas D, Guillemin F, Bezdetnaya L. Relationship between subcellular localisation of Foscan® and caspase activation in photosensitised MCF-7 cells. Br J Cancer. 2007;96(6):944-51. https://doi.org/10.1038/sj.bjc.6603631 PMid:17325708 DOI: https://doi.org/10.1038/sj.bjc.6603631

Dobson J, de Queiroz GF, Golding JP. Photodynamic therapy and diagnosis: Principles and comparative aspects. Vet J. 2018;233:8-18. https://doi.org/10.1016/j.tvjl.2017.11.012 PMid:29486883 DOI: https://doi.org/10.1016/j.tvjl.2017.11.012

Meier D, Botter SM, Campanile C, Robl B, Gräfe S, Pellegrini G, et al. Foscan and foslip based photodynamic therapy in osteosarcoma in vitro and in intratibial mouse models. Int J Cancer. 2017;140(7):1680-92. https://doi.org/10.1002/ijc.30572 PMid:27943293 DOI: https://doi.org/10.1002/ijc.30572

Spikes JD, Bommer JC. Photosensitizing properties of mono-L-aspartyl chlorin e6 (NPe6): A candidate sensitizer for the photodynamic therapy of tumors. J Photochem Photobiol B. 1993;17(2):135-43. https://doi.org/10.1016/1011-1344(93)80006-u PMid:8459317 DOI: https://doi.org/10.1016/1011-1344(93)80006-U

Yumita N, Iwase Y, Nishi K, Ikeda T, Komatsu H, Fukai T, et al. Sonodynamically-induced antitumor effect of mono-l-aspartyl chlorin e6 (NPe6). Anticancer Res 2011;31(2):501-6.

Aizawa K, Okunaka T, Ohtani T, Kawabe H, Yasunaka Y, O’Hata S, et al. Localization of mono-L-aspartyl chlorin e6 (NPe6) in mouse tissues. Photochem Photobiol. 1987;46(5):789-93. https://doi.org/10.1111/j.1751-1097.1987.tb04849.x PMid:3441501 DOI: https://doi.org/10.1111/j.1751-1097.1987.tb04849.x

Ferreira S, Juliana Menezes PF, Kurachi C, Sibata C, Allison RR, Bagnato V. Photostability of different chlorine photosensitizers. Laser Phys Lett. 2008;5:156-61. DOI: https://doi.org/10.1002/lapl.200710099

Mirzaei H, Djavid GE, Hadizadeh M, Jahanshiri-Moghadam M, Hajian P. The efficacy of Radachlorin-mediated photodynamic therapy in human hepatocellular carcinoma cells. J Photochem Photobiol B. 2015;142:86-91. https://doi.org/10.1016/j.jphotobiol.2014.11.007 PMid:25528192 DOI: https://doi.org/10.1016/j.jphotobiol.2014.11.007

Ghoodarzi R, Changizi V, Montazerabadi AR, Eyvazzadaeh N. Assessing of integration of ionizing radiation with Radachlorin- PDT on MCF-7 breast cancer cell treatment. Lasers Med Sci. 2016;31(2):213-9. https://doi.org/10.1007/s10103-015-1844-0 PMid:26690358 DOI: https://doi.org/10.1007/s10103-015-1844-0

Kochneva EV, Filonenko EV, Vakulovskaya EG, Scherbakova EG, Seliverstov OV, Markichev NA, et al. Photosensitizer radachlorin®: Skin cancer PDT phase II clinical trials. Photodiagnosis Photodyn Ther. 2010;7(4):258-67. https://doi.org/10.1016/j.pdpdt.2010.07.006 PMid:21112549 DOI: https://doi.org/10.1016/j.pdpdt.2010.07.006

Anand S, Rollakanti KR, Brankov N, Brash DE, Hasan T, Maytin EV. Fluorouracil enhances photodynamic therapy of squamous cell carcinoma via a p53-independent mechanism that increases protoporphyrin IX levels and tumor cell death. Mol Cancer Ther. 2017;16(6):1092-101. https://doi.org/10.1158/1535-7163.MCT-16-0608 PMid:28336806 DOI: https://doi.org/10.1158/1535-7163.MCT-16-0608

Gijsens A, De Witte P. Photocytotoxic action of EGF-PVA-Sn(IV) chlorin e6 and EGF-dextran-Sn(IV)chlorin e6 internalizable conjugates on A431 cells. Int J Oncol. 1998;13(6):1171-7. https://doi.org/10.3892/ijo.13.6.1171 PMid:9824627 DOI: https://doi.org/10.3892/ijo.13.6.1171

Brasseur N, Ouellet R, La Madeleine C, van Lier JE. Water- soluble aluminium phthalocyanine-polymer conjugates for PDT: Photodynamic activities and pharmacokinetics in tumour- bearing mice. Br J Cancer. 1999;80(10):1533-41. https://doi.org/10.1038/sj.bjc.6690557 PMid:10408394 DOI: https://doi.org/10.1038/sj.bjc.6690557

Bonnett R, Djelal BD, Nguyen A. Physical and chemical studies related to the development of m‐THPC (FOSCAN®) for the photodynamic therapy (PDT) of tumours. J. Porphyrins Phthalocyanines. 2001;5:652-61. DOI: https://doi.org/10.1002/jpp.377.abs

Sibata CH, Colussi VC, Oleinick NL, Kinsella TJ. Photodynamic therapy: A new concept in medical treatment. Braz J Med Biol Res. 2000;33(8):869-80. https://doi.org/10.1590/s0100-879x2000000800002 PMid:11023333 DOI: https://doi.org/10.1590/S0100-879X2000000800002

Zhang J, Jiang C, Figueiró Longo JP, Azevedo RB, Zhang H, Muehlmann LA. An updated overview on the development of new photosensitizers for anticancer photodynamic therapy. Acta Pharm Sin B. 2018;8(2):137-46. https://doi.org/10.1016/j.apsb.2017.09.003 PMid:29719775 DOI: https://doi.org/10.1016/j.apsb.2017.09.003

Allison RR, Bagnato VS, Cuenca R, Downie GH, Sibata CH. The future of photodynamic therapy in oncology. Future Oncol. 2006;2(1):53-71. https://doi.org/10.2217/14796694.2.1.53 PMid:16556073 DOI: https://doi.org/10.2217/14796694.2.1.53

Busch T, Cengel KA, Finlay J. Pheophorbide a as a photosensitizer in photodynamic therapy: In vivo considerations. Cancer Biol Ther. 2009;8(6):540-2. https://doi.org/10.4161/ cbt.8.6.8067 PMid:19252412 DOI: https://doi.org/10.4161/cbt.8.6.8067

Mojzisova H, Bonneau S, Vever-Bizet C, Brault D. Cellular uptake and subcellular distribution of chlorin e6 as functions of pH and interactions with membranes and lipoproteins. Biochim Biophys Acta. 2007;1768(11):2748-56. https://doi.org/10.1016/j.bbamem.2007.07.002 PMid:17692283 DOI: https://doi.org/10.1016/j.bbamem.2007.07.002

Shim G, Lee S, Kim YB, Kim CW, Oh YK. Enhanced tumor localization and retention of chlorin e6 in cationic nanolipoplexes potentiate the tumor ablation effects of photodynamic therapy. Nanotechnology. 2011;22(36):365101. https://doi.org/10.1088/0957-4484/22/36/365101 PMid:21841215 DOI: https://doi.org/10.1088/0957-4484/22/36/365101

Battersby AR. Tetrapyrroles: The pigments of life. Nat Prod Rep. 2000;17(6):507-26. https://doi.org/10.1039/b002635m PMid:11152419 DOI: https://doi.org/10.1039/b002635m

Li Z, Wang C, Cheng L, Gong H, Yin S, Gong Q, et al. PEG- functionalized iron oxide nanoclusters loaded with chlorin e6 for targeted, NIR light induced, photodynamic therapy. Biomaterials. 2013;34(36):9160-70. https://doi.org/10.1016/j.biomaterials.2013.08.041 PMid:24008045 DOI: https://doi.org/10.1016/j.biomaterials.2013.08.041

Sun L, Li Q, Hou M, Gao Y, Yang R, Zhang L, et al. Light- activatable Chlorin e6 (Ce6)-imbedded erythrocyte membrane vesicles camouflaged Prussian blue nanoparticles for synergistic photothermal and photodynamic therapies of cancer. Biomater Sci. 2013;6(11):2881-95. https://doi.org/10.1039/c8bm00812d PMid:30192355 DOI: https://doi.org/10.1039/C8BM00812D

Kostenich GA, Zhuravkin IN, Zhavrid EA. Experimental grounds for using chlorin e6 in the photodynamic therapy of malignant tumors. J Photochem Phtobiol B. 1994;22(3):211-7. https://doi.org/10.1016/1011-1344(93)06974-8 PMid:8014753 DOI: https://doi.org/10.1016/1011-1344(93)06974-8

Brockmann H, Haschad MN, Maier K, et al. About hypericin, the photodynamically active dye from Hypericum perforatum. Nat Sci. 1939;27:550. DOI: https://doi.org/10.1007/BF01495453

Abels C, Szeimies RM, Steinbach P, Richert C, Goetz AE. Targeting of the tumor microcirculation by photodynamic therapy with a synthetic porphycene. J Photochem Photobiol B. 1997;40(3):305-12. https://doi.org/10.1016/ s1011-1344(97)00074-2 PMid:9372621 DOI: https://doi.org/10.1016/S1011-1344(97)00074-2

Blant SA, Woodtli A, Wagnières G, Fontolliet C, van den Bergh H, Monnier P. In vivo fluence rate effect in photodynamic therapy of early cancers with tetra(m-hydroxyphenyl) chlorin. Photochem Photobiol. 1996;64(6):963-8. https://doi.org/10.1111/j.1751-1097.1996.tb01862.x PMid:8972639 DOI: https://doi.org/10.1111/j.1751-1097.1996.tb01862.x

Ahmad N, Gupta S, Feyes DK, Mukhtar H. Involvement of Fas (APO-l/CD-95) during photodynamic-therapy-mediated apoptosis in human epidermoid carcinoma A431 cells. J Invest Dermatol. 2006;115(6):1041-6. https://doi.org/10.1046/j.1523-1747.2000.00147.x PMid:11121139 DOI: https://doi.org/10.1046/j.1523-1747.2000.00147.x

Lam M, Oleinick NL, Nieminen AL. Photodynamic therapy- induced apoptosis in epidermoid carcinoma cells. Reactive oxygen species and mitochondrial inner membrane permeabilization. J Biol Chem. 2001;276(50):47379-86. https://doi.org/10.1074/jbc.M107678200 PMid:11579101 DOI: https://doi.org/10.1074/jbc.M107678200

Xu NF, Li JF, Cao EH, Wang JZ. Direct observation of dynamic process of cellular uptake of hypocrellin A in HeLa cells. Acta Bio Physica Sinica. 1995;11:261-6.

Miller GG, Brown K and Ballengrud AM. Preclinical assessment of Hypocrellins and hypocrellin B derivatives as sensitizers for photodynamic therapy of cancer: Progress update. Photochem Photobiol. 1995;65:714-22. DOI: https://doi.org/10.1111/j.1751-1097.1997.tb01915.x

Lavie G, Mazur Y, Lavie D, Meruelo D. The chemical and biological properties of hypericin--a compound with a broad spectrum of biological activities. Med Res Rev. 1995;15(2):111- 9. https://doi.org/10.1002/med.2610150203 PMid:7739292 DOI: https://doi.org/10.1002/med.2610150203

Miller GG, Brown K, Moore RB, Diwu ZJ, Liu J, Huang L, et al. Uptake kinetics and intracellular localization of hypocrellin photosensitizer for photodynamic therapy: Preclinical assessment of Hypocrellin A and Hypocrellin B as sensitizers for PDT of cancers. Photochem Photobiol. 1995;61(6):632-638. https://doi.org/10.1111/j.1751-1097.1995.tb09880.x PMid: 7568409

Miller GG, Brown K, Moore RB, Diwu ZJ, Liu J, Huang L, et al. Uptake kinetics and intracellular localization of hypocrellin photosensitizer for photodynamic therapy: A confocal microscopy study. Photochem Photobiol. 1995;61(6):632-8. https://doi.org/10.1111/j.1751-1097.1995.tb09880.x PMid:7568409 DOI: https://doi.org/10.1111/j.1751-1097.1995.tb09880.x

Dong CY, Jia HT, Ma CM. The inhibitory effect of the new photosensitizer hypocrellin A on experimental tumors. Chin J Biochem. 1987;20:468-72.

Kamuhabwa AR, Agostinis P, D’Hallewin MA, Kasran A, de Witte PA. Photodynamic activity of hypericin in human urinary bladder carcinoma cells. Anticancer Res. 2000;20(4):2579-84.

Hudson JB, Zhou J, Chen J, Harris L, Yip L, Towers GH. Hypocrellin, from Hypocrella bambuase, is phototoxic to human immunodeficiency virus. Photochem Photobiol. 1994;60(3):253- 5. https://doi.org/10.1111/j.1751-1097.1994.tb05100.x PMid:7972377 DOI: https://doi.org/10.1111/j.1751-1097.1994.tb05100.x

Hirayama J, Ikebuchi K, Abe H, Kwon KW, Ohnishi Y, Horiuchi M, et al. Photoactivation of virus infectivity by hypocrellin A. Photochem Photobiol. 1997;66:697-700. DOI: https://doi.org/10.1111/j.1751-1097.1997.tb03209.x

Diwu Z, Lown JW. Photosensitization by anticancer agents 12. Perylene quinonoid pigments, a novel type of singlet oxygen sensitizer. J Photochem Photobiol Chem. 1992;64(3):273-87. https://doi.org/10.1016/1010-6030(92)85002-C DOI: https://doi.org/10.1016/1010-6030(92)85002-C

Kitanov GM. Hypericin and pseudohypericin in some Hypericum species. Biochem Syst Ecol. 2001;29(2):171-8. https://doi.org/10.1016/s0305-1978(00)00032-6 PMid:11106845 DOI: https://doi.org/10.1016/S0305-1978(00)00032-6

Ayan AK, Cirak C, Kevseroglu K, Ozen T. Hypericin in some Hypericum species from Turkey. Asian J Plant Sci. 2004;3:200-2. DOI: https://doi.org/10.3923/ajps.2004.200.202

Dewick PM. Medicinal Natural Products: A Biosynthetic Approach. 2nd ed. Chichester: John Wiley & Sons Ltd.; 2002. DOI: https://doi.org/10.1002/0470846275

Garnica S, Weiss M, Oberwinkler F. Morphological and molecular phylogenetic studies in South American Cortinarius species. Mycol Res. 2003;107(Pt 10):1143-56. https://doi.org/10.1017/s0953756203008414 PMid:14635763 DOI: https://doi.org/10.1017/S0953756203008414

Kusari S, Lamshöft M, Zühlke S, Spiteller M. An endophytic fungus from Hypericum perforatum that produces hypericin. J Nat Prod. 2008;71(2):159-62. https://doi.org/10.1021/np070669k PMid:18220354 DOI: https://doi.org/10.1021/np070669k

Kusari S, Zühlke S, Kosuth J, Cellárová E, Spiteller M. Light-independent metabolomics of endophytic Thielavia subthermophila provides insight into microbial hypericin biosynthesis. J Nat Prod. 2009;72(10):1825-35. https://doi.org/10.1021/np9002977 PMid:19746917 DOI: https://doi.org/10.1021/np9002977

Kucharíková A, Kimáková K, Janfelt C, Čellárová E. Interspecific variation in localization of hypericins and phloroglucinols in the genus Hypericum as revealed by desorption electrospray ionization mass spectrometry imaging. Physiol Plant. 2016;157(1):2-12. http://doi.org/10.1111/ppl.12422 PMid:26822391 DOI: https://doi.org/10.1111/ppl.12422

Cellárová E. Effect of exogenous morphogenetic signals on ˇ differentiation in vitro and secondary metabolite formation in the genus Hypericum. In: Odabas MS, Çırak C, editors. Medicinal and Aromatic Plant Science and Biotechnology 5 (Special Issue 1). Ikenobe: Global Science Books; 2011. p. 62-9.

Košuth J, Koperdáková J, Tolonen A, Hohtola A, Cellárová E. The content of hypericins and phloroglucinols in Hypericum perforatum L. seedlings at early stage of development. Plant Sci. 2003;165:515-21. DOI: https://doi.org/10.1016/S0168-9452(03)00210-3

Urbanová M, Kosuth J, Cellárová E. Genetic and biochemical analysis of Hypericum perforatum L. plants regenerated after cryopreservation. Plant Cell Rep. 2006;25(2):140-7. https://doi.org/10.1007/s00299-005-0050-0 PMid:16456647 DOI: https://doi.org/10.1007/s00299-005-0050-0

Brunáková K, Petijová L, Zámecník J, Turecková V, Cellárová E. The role of ABA in the freezing injury avoidance in two Hypericum species differing in frost tolerance and potential to synthesize hypericins. Plant Cell Tissue Organ Cult. 2015;122:45-56. DOI: https://doi.org/10.1007/s11240-015-0748-9

Bhuvaneswari R, Gan YY, Yee KK, Soo KC, Olivo M. Effect of hypericin-mediated photodynamic therapy on the expression of vascular endothelial growth factor in human nasopharyngeal carcinoma. Int J Mol Med. 2007;20(4):421-8. DOI: https://doi.org/10.3892/ijmm.20.4.421

Olivo M, Du HY, Bay BH. Hypericin lights up the way for the potential treatment of nasopharyngeal cancer by photodynamic therapy. Curr Clin Pharmacol. 2006;1(3):217-22. https://doi.org/10.2174/157488406778249370 PMid:18666746 DOI: https://doi.org/10.2174/157488406778249370

Kaihong Z, Lijin J. Conversion of Hypocrellin A in alkaline and neutral media. Chin J Org Chem. 1989;9:252.

Estey EP, Brown K, Diwu Z, Liu J, Lown JW, Miller GG, et al. Hypocrellins as photosensitizers for photodynamic therapy: A screening evaluation and pharmacokinetic study. Cancer Chemother Pharmacol. 1996;37(4):343-50. https://doi.org/10.1007/s002800050395 PMid:8548880 DOI: https://doi.org/10.1007/s002800050395

Zhenjun D, Lown JW. Hypocrellins and their use in photosensitization. Photochem Photobiol. 1990;52(3):609-16. https://doi.org/10.1111/j.1751-1097.1990.tb01807.x PMid:2284353 DOI: https://doi.org/10.1111/j.1751-1097.1990.tb01807.x

Wakdikar S. Global health care challenge: Indian experiences and new prescriptions. Electron J Biotechnol. 2004;7:214-20. DOI: https://doi.org/10.2225/vol7-issue3-fulltext-5

Bhutani KK, Gohil VM. Natural products drug discovery research in India: Status and appraisal. Indian J Exp Biol. 2010;48(3):199-207.

Zhang HA, Kitts DD. Turmeric and its bioactive constituents trigger cell signaling mechanisms that protect against diabetes and cardiovascular diseases. Mol Cell Biochem. 2021;476(10):3785- 814. https://doi.org/10.1007/s11010-021-04201-6 PMid:34106380 DOI: https://doi.org/10.1007/s11010-021-04201-6

Rathaur P, Raja W, Ramteke PW, Suchit AJ. Turmeric: The golden spice of life. Int J Pharm Sci Res. 2012;3:1987-94.

Tung BT, Nham DT, Hai NT, Thu DK. Curcuma longa, the Polyphenolic curcumin compound and pharmacological effects on liver. In: Watson RR, Preedy VR, editors. Dietary Interventions in Liver Disease. Ch. 10. Cambridge, MA, USA: Academic Press; 2019. p. 125-34. DOI: https://doi.org/10.1016/B978-0-12-814466-4.00010-0

Kazantzis KT, Koutsonikoli K, Mavroidi B, Zachariadis M, Alexiou P, Pelecanou M., Politopoulos K, et al. Curcumin derivatives as photosensitizers in photodynamic therapy: Photophysical properties and in vitro studies with prostate cancer cells. Photochem Photobiol Sci. 2010;19:193-206. DOI: https://doi.org/10.1039/c9pp00375d

Dahl TA, McGowan WM, Shand MA, Srinivasan VS. Photokilling of bacteria by the natural dye curcumin. Arch Microbiol. 1989;151(2):183-5. https://doi.org/10.1007/BF00414437 PMid:2655550 DOI: https://doi.org/10.1007/BF00414437

Haukvik T, Bruzell E, Kristensen S, Tønnesen HH. Photokilling of bacteria by curcumin in selected polyethylene glycol 400 (PEG

preparations. Studies on curcumin and curcuminoids, XLI. Pharmazie. 2010;65(8):600-6.

Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, et al. Photodynamic therapy. J Natl Cancer Inst. 1998;90:889-905. DOI: https://doi.org/10.1093/jnci/90.12.889

Gupta S, Dwarakanath BS, Muralidhar K, Koru-Sengul T, Jain V. Non-monotonic changes in clonogenic cell survival induced by disulphonated aluminum phthalocyanine photodynamic treatment in a human glioma cell line. J Transl Med. 2010;8:43. https://doi.org/10.1186/1479-5876-8-43 PMid:20433757 DOI: https://doi.org/10.1186/1479-5876-8-43

Oleinick NL, Morris RL, Belichenko I. The role of apoptosis in response to photodynamic therapy: What, where, why, and how. Photochem Photobiol Sci. 2002;1(1):1-21. https://doi.org/10.1039/b108586g PMid:12659143 DOI: https://doi.org/10.1039/b108586g

Zhu TC, Finlay JC. The role of photodynamic therapy (PDT) physics. Med Phys. 2008;35(7):3127-36. https://doi. org/10.1118/1.2937440 PMid:18697538 DOI: https://doi.org/10.1118/1.2937440

Postiglione I, Chiaviello A, Palumbo G. Enhancing photodynamyc therapy efficacy by combination therapy: Dated, current and oncoming strategies. Cancers (Basel). 2011;3(2):2597-629. https://doi.org/10.3390/cancers3022597 PMid:24212824 DOI: https://doi.org/10.3390/cancers3022597

Misiewicz K, Skupińska K, Graczyk A, Kasprzycka-Guttman T. Influence of protoporphyrin IX amino acid substituents on affinity to human breast adenocarcinoma MCF-7 cells. Biotechnic Histochem. 2009;84(1):17-23. DOI: https://doi.org/10.1080/10520290802673381

Morgan J, Oseroff AR. Mitochondria-based photodynamic anti- cancer therapy. Adv Drug Deliv Rev. 2001;49(1-2):71-86. https://doi.org/10.1016/s0169-409x(01)00126-0 PMid:11377804 DOI: https://doi.org/10.1016/S0169-409X(01)00126-0

Merlin JL, Gautier H, Barberi-Heyob M, Teiten MH, Guillemin F. The multidrug resistance modulator SDZ-PSC 833 potentiates the photodynamic activity of chlorin e6 independently of P-glycoprotein in multidrug resistant human breast adenocarcinoma cells. Int J Oncol. 2003;22(4):733-9. DOI: https://doi.org/10.3892/ijo.22.4.733

Li Y, Yu Y, Kang L, Lu Y. Effects of chlorin e6-mediated photodynamic therapy on human colon cancer SW480 cells. Int J Clin Exp Med. 2014;7(12):4867-76.

Kessel D, Poretz RD. Sites of photodamage induced by photodynamic therapy with a chlorin e6 triacetoxymethyl ester (CAME). Photochem Photobiol. 2000;71(1):94-6. https://doi. org/10.1562/0031-8655(2000)071<0094:sopibp>2.0.co;2 PMid:10649895 DOI: https://doi.org/10.1562/0031-8655(2000)0710094SOPIBP2.0.CO2

Kessel D, Woodburn K, Gomer CJ, Jagerovic N, Smith KM. Photosensitization with derivatives of chlorin p6. J Photochem Photobiol B. 1995;28(1):13-8. https://doi.org/10.1016/1011-1344(94)07085-3 PMid:7791001 DOI: https://doi.org/10.1016/1011-1344(94)07085-3

Broekgaarden M, Weijer R, van Gulik TM, Hamblin MR, Heger M. Tumor cell survival pathways activated by photodynamic therapy: A molecular basis for pharmacological inhibition strategies. Cancer Metastasis Rev. 2015;34(4):643- 90. https://doi.org/10.1007/s10555-015-9588-7 PMid:26516076 DOI: https://doi.org/10.1007/s10555-015-9588-7

Dang J, He H, Chen D, Yin L. Manipulating tumor hypoxia toward enhanced photodynamic therapy (PDT). Biomater Sci. 2017;5(8):1500-11. https://doi.org/10.1039/c7bm00392g PMid:28681887 DOI: https://doi.org/10.1039/C7BM00392G

van Straten D, Mashayekhi V, de Bruijn HS, Oliveira S, Robinson DJ. Oncologic photodynamic therapy: Basic principles, current clinical status and future directions. Cancers (Basel). 2017;9(2):19. https://doi.org/10.3390/cancers9020019 PMid:28218708 DOI: https://doi.org/10.3390/cancers9020019

Elmore S. Apoptosis: A review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516. https://doi.org/10.1080/01926230701320337 PMid:17562483 DOI: https://doi.org/10.1080/01926230701320337

Moon YH, Kwon SM, Kim HJ, Jung KY, Park JH, Kim SA, et al. Efficient preparation of highly pure chlorin e6 and its photodynamic anti-cancer activity in a rat tumor model. Oncol Rep. 2009;22(5):1085-91. DOI: https://doi.org/10.3892/or_00000540