Current view on photodynamic therapy in medicine

Abstract

Light has been used for medical purposes for centuries, but the first steps toward photodynamic therapy (PDT) were taken in the early 20th century. PDT is an innovative therapeutic approach that involves three key components: A photosensitizer (PS), molecular oxygen, and visible light. The destruction of diseased tissues and cells in PDT occurs through the activation of a PS by near-infrared or visible radiation. This activation, in the presence of molecular oxygen, generates singlet oxygen and other reactive oxygen species. PDT has been successfully applied to treat various types of cancer, particularly superficial ones. This review outlines the principles of PDT and discusses its application in cancer treatment, specifically in the context of pancreatic and esophageal cancer. While PDT is effective, it can also have adverse effects on the human body, such as changes to cell and organelle membranes. PDT is a modern, non-invasive treatment modality utilized for both non-malignant conditions and also various types of tumors in diverse locations. Enhancing the efficacy of PDT and reducing its side effects may be possible by combining PSs with nanomaterials, which would also allow for targeted therapy to specific receptors. PDT is continuously being developed to improve its effectiveness, and ongoing studies aim to minimize unwanted side effects and identify contraindications for its use.

Keywords

Photodynamic therapy / Photosensitizers / Pancreas / Esophagus

Funding

None.

Conflict of interest

The authors declare that they have no competing interests.

References

[1] Kessel D. Photodynamic therapy: A brief history. J Clin Med. 2019; 8(10):1581. doi: 10.3390/jcm8101581

[2] Chilakamarthi U, Giribabu L. Photodynamic therapy: Past, present and future. Chem Rec. 2017; 17(8):775-802. doi: 10.1002/tcr.201600121

[3] Nowis D, Makowski M, Stokłosa T, Legat M, Issat T, Gołab J. Direct tumor damage mechanisms of photodynamic therapy. Acta Biochim Pol. 2005; 52(2):339-352.

[4] Kwiatkowski S, Knap B, Przystupski D, et al. Photodynamic therapy - mechanisms, photosensitizers and combinations. Biomed Pharmacother. 2018; 106:1098-1107. doi: 10.1016/j.biopha.2018.07.049

[5] Luketich JD, Christie NA, Buenaventura PO, Weigel TL, Keenan RJ, Nguyen NT. Endoscopic photodynamic therapy for obstructing esophageal cancer: 77 cases over a 2-year period. Surg Endosc. 2000; 14(7):653-657. doi: 10.1007/s004640000144

[6] Bown SG, Rogowska AZ, Whitelaw DE, et al. Photodynamic therapy for cancer of the pancreas. Gut. 2002; 50(4):549-557. doi: 10.1136/gut.50.4.549

[7] Abulafi AM, Allardice JT, Williams NS, van Someren N, Swain CP, Ainley C. Photodynamic therapy for malignant tumours of the ampulla of Vater. Gut. 1995; 36(6):853-856. doi: 10.1136/gut.36.6.853

[8] van Duijnhoven FH, Rovers JP, Engelmann K, et al. Photodynamic therapy with 5,10,15,20-tetrakis(m-hydroxyphenyl) bacteriochlorin for colorectal liver metastases is safe and feasible: Results from a phase I study. Ann Surg Oncol. 2005; 12(10):808-816. doi: 10.1245/ASO.2005.09.005

[9] DeWitt JM, Sandrasegaran K, O’Neil B, et al. Phase 1 study of EUS-guided photodynamic therapy for locally advanced pancreatic cancer. Gastrointest Endosc. 2019; 89(2):390-398. doi: 10.1016/j.gie.2018.09.007

[10] Yano T, Wang KK. Photodynamic therapy for gastrointestinal cancer. Photochem Photobiol. 2020; 96(3):517-523. doi: 10.1111/php.13206

[11] Huggett MT, Jermyn M, Gillams A, et al. Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer. Br J Cancer. 2014; 110(7):1698-1704. doi: 10.1038/bjc.2014.95

[12] Lightdale CJ, Heier SK, Marcon NE, et al. Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd: YAG laser for palliation of esophageal cancer: A multicenter randomized trial. Gastrointest Endosc. 1995; 42(6):507-512. doi: 10.1016/s0016-5107(95)70002-1

[13] Kashtan H, Konikoff F, Haddad R, Skornick Y. Photodynamic therapy of cancer of the esophagus using systemic aminolevulinic acid and a non laser light source: A phase I/ II study. Gastrointest Endosc. 1999; 49(6):760-764. doi: 10.1016/s0016-5107(99)70297-x

[14] Kato H, Horai T, Furuse K, et al. Photodynamic therapy for cancers: A clinical trial of porfimer sodium in Japan. Jpn J Cancer Res. 1993; 84(11):1209-1214. doi: 10.1111/j.1349-7006.1993.tb02823.x

[15] Maier A, Tomaselli F, Matzi V, Rehak P, Pinter H, Smolle-Jüttner FM. Does new photosensitizer improve photodynamic therapy in advanced esophageal carcinoma? Lasers Surg Med. 2001; 29(4):323-327. doi: 10.1002/lsm.1124

[16] Da Cruz Andrade PV, Euzebio Alves VT, de Carvalho VF, et al. Photodynamic therapy decrease immune-inflammatory mediators levels during periodontal maintenance. Lasers Med Sci. 2017; 32(1):9-17. doi: 10.1007/s10103-016-2076-7

[17] Kelty CJ, Ackroyd R, Brown NJ, Stephenson TJ, Stoddard CJ, Reed MW. Endoscopic ablation of Barrett’s oesophagus: A randomized-controlled trial of photodynamic therapy vs. argon plasma coagulation. Aliment Pharmacol. 2004; 20(11- 12):1289-1296. doi: 10.1111/j.1365-2036.2004.02277.x

[18] Kohoutova D, Haidry R, Banks M, et al. Long-term outcomes of the randomized controlled trial comparing 5-aminolaevulinic acid and Photofrin photodynamic therapy for Barrett’s oesophagus related neoplasia. Scand J Gastroenterol. 2018; 53(5):527-532. doi: 10.1080/00365521.2017.1403646

[19] Ackroyd R, Brown NJ, Davis MF, et al. Photodynamic therapy for dysplastic Barrett’s oesophagus: A prospective, double blind, randomised, placebo controlled trial. Gut. 2000; 47(5):612-617. doi: 10.1136/gut.47.5.612

[20] Gray J, Fullarton GM. Long term efficacy of Photodynamic Therapy (PDT) as an ablative therapy of high grade dysplasia in Barrett’s oesophagus. Photodiagnosis Photodyn Ther. 2013; 10(4):561-565. doi: 10.1016/j.pdpdt.2013.06.002

[21] Hage M, Siersema PD, van Dekken H, et al. 5-aminolevulinic acid photodynamic therapy versus argon plasma coagulation for ablation of Barrett’s oesophagus: A randomised trial. Gut. 2004; 53(6):785-790. doi: 10.1136/gut.2003.028860

[22] Kim EJ, Mangold AR, DeSimone JA, et al. Efficacy and safety of topical hypericin photodynamic therapy for early-stage cutaneous T-cell lymphoma (mycosis fungoides): The FLASH phase 3 randomized clinical trial. JAMA Dermatol. 2022; 158(9):1031-1039. doi: 10.1001/jamadermatol.2022.2749

[23] Séguier S, Souza SL, Sverzut AC, et al. Impact of photodynamic therapy on inflammatory cells during human chronic periodontitis. J Photochem Photobiol B. 2010; 101(3):348-354. doi: 10.1016/j.jphotobiol.2010.08.007

[24] Wu C, Qiu X, He C, Ci C. Effect of 5-aminolevulinic acid photodynamic therapy with transfer factor capsules in the treatment of multiple plantar warts. Biomed Res Int. 2022;2022:1220889. doi: 10.1155/2022/1220889

[25] Theodoraki MN, Lorenz K, Lotfi R, et al. Influence of photodynamic therapy on peripheral immune cell populations and cytokine concentrations in head and neck cancer. Photodiagnosis Photodyn Ther. 2017; 19:194-201. doi: 10.1016/j.pdpdt.2017.05.015

[26] Thanos SM, Halliday GM, Damian DL. Nicotinamide reduces photodynamic therapy-induced immunosuppression in humans. Br J Dermatol. 2012; 167(3):631-636. doi: 10.1111/j.1365-2133.2012.11109.x

[27] De Moraes M, de Vasconcelos RC, Longo JP, et al. Effects of photodynamic therapy mediated by nanoemulsion containing chloro-aluminum phthalocyanine: A histologic and immunohistochemical study in human gingiva. Photodiagnosis Photodyn Ther. 2015; 12(4):592-597. doi: 10.1016/j.pdpdt.2015.10.009

[28] Evangelou G, Farrar MD, Cotterell L, et al. Topical photodynamic therapy significantly reduces epidermal Langerhans cells during clinical treatment of basal cell carcinoma. Br J Dermatol. 2012; 166(5):1112-1115. doi: 10.1111/j.1365-2133.2012.10823.x

[29] Pourabbas R, Kashefimehr A, Rahmanpour N, Babaloo Z, Kishen A, Tenenbaum HC. Effects of photodynamic therapy on clinical and gingival crevicular fluid inflammatory biomarkers in chronic periodontitis: A split-mouth randomized clinical trial. J Periodontol. 2014; 85(9):1222-1229. doi: 10.1902/jop.2014.130464

[30] Wang KK, Lutzke L, Borkenhagen L, et al. Photodynamic therapy for Barrett’s esophagus: Does light still have a role? Endoscopy. 2008; 40(12):1021-1025. doi: 10.1055/s-0028-1103405

[31] Qi F, Yuan H, Chen Y, et al. BODIPY-based monofunctional Pt (II) complexes for specific photocytotoxicity against cancer cells. J Inorg Biochem. 2021;218:111394. doi: 10.1016/j.jinorgbio.2021.111394

[32] Koli M, Gupta S, Chakraborty S, et al. Design and Synthesis of BODIPY-Hetero[5]helicenes as Heavy-atom-free triplet photosensitizers for photodynamic therapy of cancer. Chemistry. 2023; 29(57):e202301605. doi: 10.1002/chem.202301605

[33] Elgun T, Yurttas AG, Cinar K, Ozcelik S, Gul A. Effect of aza-BODIPY-photodynamic therapy on the expression of carcinoma-associated genes and cell death mode. Photodiagnosis Photodyn Ther. 2023;44:103849. doi: 10.1016/j.pdpdt.2023.103849

[34] Zhang J, Wang N, Ji X, Tao Y, Wang J, Zhao W. BODIPY-based fluorescent probes for biothiols. Chemistry. 2020; 26(19):4172-4192. doi: 10.1002/chem.201904470

[35] Antina E, Bumagina N, Marfin Y, et al. BODIPY conjugates as functional compounds for medical diagnostics and treatment. Molecules. 2022; 27(4):1396. doi: 10.3390/molecules27041396

[36] Barattucci A, Gangemi CM, Santoro A, Campagna S, Puntoriero F, Bonaccorsi P. Bodipy-carbohydrate systems: Synthesis and bio-applications. Org Biomol Chem. 2022; 20(14):2742-2763. doi: 10.1039/d1ob02459k

[37] Das S, Dey S, Patra S, et al. BODIPY-based molecules for biomedical applications. Biomolecules. 2023; 13(12):1723. doi: 10.3390/biom13121723

[38] Ma C, Zhang T, Xie Z. Leveraging BODIPY nanomaterials for enhanced tumor photothermal therapy. J Mater Chem B. 2021; 9(36):7318-7327. doi: 10.1039/d1tb00855b

[39] Chang HJ, Bondar MV, Munera N, et al. Femtosecond spectroscopy and nonlinear optical properties of aza-BODIPY derivatives in solution. Chemistry. 2022; 28(17):e202104072. doi: 10.1002/chem.202104072

[40] Prieto-Montero R, Prieto-Castañeda A, Sola-Llano R, et al. Exploring BODIPY derivatives as singlet oxygen photosensitizers for PDT. Photochem Photobiol. 2020; 96(3):458-477. doi: 10.1111/php.13232

[41] Alvarez N, Sevilla A. Current advances in photodynamic therapy (PDT) and the future potential of PDT-combinatorial cancer therapies. Int J Mol Sci. 2024; 25(2):1023. doi: 10.3390/ijms25021023

[42] Singh N, Sen Gupta R, Bose S. A comprehensive review on singlet oxygen generation in nanomaterials and conjugated polymers for photodynamic therapy in the treatment of cancer. Nanoscale. 2024; 16(7):3243-326842. doi: 10.1039/d3nr05801h

[43] Köse GG, Erdoğmuş A. Dual effect of light and ultrasound for efficient singlet oxygen generation with novel diaxial silicon phthalocyanine sensitizer. Photochem Photobiol. 2024; 100(1):52-66. doi: 10.1111/php.13834