Generic placeholder image

Current Cancer Therapy Reviews


ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Review Article

Photodynamic Therapy of Cancer: Quality and Prospective of Therapy based on Photosensitizer

Author(s): Arun Kumar Singh, Rishabha Malviya*, Ankita Moharana, Vedant Kumar Prajapati and Ashish Kumar Nirmal

Volume 19, Issue 3, 2023

Published on: 03 March, 2023

Page: [223 - 236] Pages: 14

DOI: 10.2174/1573394719666230119142053

Price: $65


To kill cancer cells, photodynamic therapy (PDT) utilizes a light-sensitive medication and light. Light-sensitive drugs are absorbed by cancerous cells. The cells are then illuminated with a specific light or laser by a specialist and oxygen that destroys cancer cells is released. The present study aims to discuss the roles, advancements, and limitations of photodynamic therapy in cancer treatment. Photosensitizers and photosensitizing agents are used in photodynamic treatment to destroy cancer cells. Lasers or other light sources, such as LEDs, may provide illumination. There are reports of a novel nanoplatform for the treatment of HER2-overexpressed breast cancer, as well as other primary and metastatic cancers, using fluorescent electron microscopy PDT/photothermal therapy (PTT) dualtherapy. PDT has a significant benefit over conventional cancer therapies because it may cause fewer adverse effects. PDT-induced immunostimulatory cell death and the production of a robust local inflammatory response might lead to effective local anticancer therapy. PDT has a lower long-term morbidity and recovery time than surgery, chemotherapy, or radiation.

Keywords: Photodynamic therapy, photosensitizers, cell death, phototoxicity, cancer therapy, photothermal therapy.

Graphical Abstract
Bos PD, Zhang XHF, Nadal C, et al. Genes that mediate breast cancer metastasis to the brain. Nature 2009; 459(7249): 1005-9.
[] [PMID: 19421193]
Weigelt B, Peterse JL. van’t VLJ. Breast cancer metastasis: Markers and models. Nat Rev Cancer 2005; 5(8): 591-602.
[] [PMID: 16056258]
Peinado H, Zhang H, Matei IR, et al. Pre-metastatic niches: Organ-specific homes for metastases. Nat Rev Cancer 2017; 17(5): 302-17.
[] [PMID: 28303905]
Real PJ, Sierra A, de Juan A, Segovia JC, Lopez-Vega JM, Fernandez-Luna JL. Resistance to chemotherapy via Stat3-dependent overexpression of Bcl-2 in metastatic breast cancer cells. Oncogene 2002; 21(50): 7611-8.
[] [PMID: 12400004]
Daniell MD, Hill JS. A history of photodynamic therapy. ANZ J Surg 1991; 61(5): 340-8.
[] [PMID: 2025186]
Ackroyd R, Kelty C, Brown N, Reed M. The history of photodetection and photodynamic therapy. Photochem Photobiol 2001; 74(5): 656-69.
[<0656:THOPAP>2.0.CO;2] [PMID: 11723793]
Kou J, Dou D, Yang L. Porphyrin photosensitizers in photodynamic therapy and its applications. Oncotarget 2017; 8(46): 81591-603.
[] [PMID: 29113417]
Rizvi I, Celli JP, Evans CL, et al. Synergistic enhancement of carboplatin efficacy with photodynamic therapy in a three-dimensional model for micrometastatic ovarian cancer. Cancer Res 2010; 70(22): 9319-28.
[] [PMID: 21062986]
Ahn TG, Lee BR, Choi EY, Kim DW, Han SJ. Photodynamic therapy for breast cancer in a BALB/c mouse model. J Gynecol Oncol 2012; 23(2): 115-9.
[] [PMID: 22523628]
Montazerabadi AR, Sazgarnia A, Bahreyni-Toosi MH, Ahmadi A, Shakeri-Zadeh A, Aledavood A. Mitoxantrone as a prospective photosensitizer for photodynamic therapy of breast cancer. Photodiagn Photodyn Ther 2012; 9(1): 46-51.
[] [PMID: 22369728]
Agostinis P, Breyssens H, Buytaert E, Hendrickx N. Regulatory pathways in photodynamic therapy induced apoptosis. Photochem Photobiol Sci 2004; 3(8): 721-9.
[] [PMID: 15295626]
Casas A, Di Venosa G, Hasan T, Batlle A. Mechanisms of resistance to photodynamic therapy. Curr Med Chem 2011; 18(16): 2486-515.
[] [PMID: 21568910]
Klotz LO, Kröncke KD, Sies H. Singlet oxygen-induced signaling effects in mammalian cells. Photochem Photobiol Sci 2003; 2(2): 88-94.
[] [PMID: 12664966]
Gewirtz DA, Holt SE, Grant S, Eds. Apoptosis, senescence and cancer. Springer Science & Business Media 2007.
Bacellar I, Tsubone T, Pavani C, Baptista M. Photodynamic efficiency: From molecular photochemistry to cell death. Int J Mol Sci 2015; 16(9): 20523-59.
[] [PMID: 26334268]
Jensen TJ, Vicente MGH, Luguya R, Norton J, Fronczek FR, Smith KM. Effect of overall charge and charge distribution on cellular uptake, distribution and phototoxicity of cationic porphyrins in HEp2 cells. J Photochem Photobiol B 2010; 100(2): 100-11.
[] [PMID: 20558079]
Pavani C, Iamamoto Y, Baptista MS. Mechanism and efficiency of cell death of type II photosensitizers: Effect of zinc chelation. Photochem Photobiol 2012; 88(4): 774-81.
[] [PMID: 22283143]
Bacellar IOL, Oliveira MC, Dantas LS, et al. Photosensitized membrane permeabilization requires contact-dependent reactions between photosensitizer and lipids. J Am Chem Soc 2018; 140(30): 9606-15.
[] [PMID: 29989809]
Allison RR, Downie GH, Cuenca R, Hu XH, Childs CJH, Sibata CH. Photosensitizers in clinical PDT. Photodiagn Photodyn Ther 2004; 1(1): 27-42.
Beyer W. Systems for light application and dosimetry in photodynamic therapy. J Photochem Photobiol B 1996; 36(2): 153-6.
[] [PMID: 9002252]
Wilson BC, Patterson MS. The physics, biophysics and technology of photodynamic therapy. Phys Med Biol 2008; 53(9): R61-R109.
[] [PMID: 18401068]
Plaetzer K, Krammer B, Berlanda J, Berr F, Kiesslich T. Photophysics and photochemistry of photodynamic therapy: Fundamental aspects. Lasers Med Sci 2009; 24(2): 259-68.
[] [PMID: 18247081]
Foote CS. Mechanisms of photosensitized oxidation. There are several different types of photosensitized oxidation which may be important in biological systems. Science 1968; 162(3857): 963-70.
[] [PMID: 4972417]
Dysart JS, Patterson MS. Characterization of Photofrin photobleaching for singlet oxygen dose estimation during photodynamic therapy of MLL cells in vitro. Phys Med Biol 2005; 50(11): 2597-616.
[] [PMID: 15901957]
Moan J, Berg K, Kvam E, et al. Intracellular localization of photosensitizers. Ciba Found Symp 1989; 146: 95-107.
[PMID: 2697539]
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.
[PMID: 17693025]
Kessel D, Castelli M. Evidence that bcl-2 is the target of three photosensitizers that induce a rapid apoptotic response. Photochem Photobiol 2001; 74(2): 318-22.
[<0318:ETBITT>2.0.CO;2] [PMID: 11547571]
Xue L, Chiu S, Oleinick NL. Photochemical destruction of the Bcl-2 oncoprotein during photodynamic therapy with the phthalocyanine photosensitizer Pc 4. Oncogene 2001; 20(26): 3420-7.
[] [PMID: 11423992]
Usuda J, Chiu S, Murphy ES, Lam M, Nieminen AL, Oleinick NL. Domain-dependent photodamage to Bcl-2. A membrane anchorage region is needed to form the target of phthalocyanine photosensitization. J Biol Chem 2003; 278(3): 2021-9.
[] [PMID: 12379660]
Berg K, Moan J. Lysosomes as photochemical targets. Int J Cancer 1994; 59(6): 814-22.
[] [PMID: 7989124]
Reiners JJ Jr, Caruso JA, Mathieu P, Chelladurai B, Yin X-M, Kessel D. Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves bid cleavage. Cell Death Differ 2002; 9(9): 934-44.
[] [PMID: 12181744]
Kessel D. Relocalization of cationic porphyrins during photodynamic therapy. Photochem Photobiol Sci 2002; 1(11): 837-40.
[] [PMID: 12659521]
Tokura Y, Seo N, Takigawa M, Fujie M. Quinolone-photoconjugated major histocompatibility complex class II-binding peptides with lysine are antigenic for T cells mediating murine quinolone photoallergy. J Invest Dermatol 2001; 117(5): 1206-11.
[] [PMID: 11710934]
Devleeschouwer V, Roelandts R, Garmyn M, Goossens A. Allergic and photoallergic contact dermatitis from ketoprofen: results of (photo) patch testing and follow-up of 42 patients. Contact Dermat 2008; 58(3): 159-66.
[] [PMID: 18279154]
Atarashi K, Kabashima K, Akiyama K, Tokura Y. Stimulation of langerhans cells with ketoprofen plus UVA in murine photocontact dermatitis to ketoprofen. J Dermatol Sci 2007; 47(2): 151-9.
[] [PMID: 17512174]
Tokura Y, Iwamoto Y, Mizutani K, Takigawa M. Sparfloxacin phototoxicity: Potential photoaugmentation by ultraviolet A and B sources. Arch Dermatol Res 1996; 288(1): 45-50.
[] [PMID: 8750934]
Hague JS, Ilchyshyn A. Lichenoid photosensitive eruption due to capecitabine chemotherapy for metastatic breast cancer. Clin Exp Dermatol 2007; 32(1): 102-3.
[PMID: 16879449]
Stein KR, Scheinfeld NS. Drug-induced photoallergic and phototoxic reactions. Expert Opin Drug Saf 2007; 6(4): 431-43.
[] [PMID: 17688387]
Seto Y, Hosoi K, Takagi H, et al. Exploratory and regulatory assessments on photosafety of new drug entities. Curr Drug Saf 2012; 7(2): 140-8.
[] [PMID: 22873498]
Ohshima A, Seo N, Takigawa M, Tokura Y. Formation of antigenic quinolone photoadducts on Langerhans cells initiates photoallergy to systemically administered quinolone in mice. J Invest Dermatol 2000; 114(3): 569-75.
[] [PMID: 10692119]
Kochevar IE. Phototoxicity mechanisms: chlorpromazine photosensitized damage to DNA and cell membranes. J Invest Dermatol 1981; 77(1): 59-64.
[] [PMID: 7252258]
Quedraogo G, Morliere P, Santus R. Miranda, Castell JV. Damage to mitochondria of cultured human skin fibroblasts photosensitized by fluoroquinolones. J PhotochemPhotobiol 2000; 58: 20-5.
[] [PMID: 11195848]
Nakamura M, Henderson M, Jacobsen G, Lim HW. Comparison of photodermatoses in African-Americans and Caucasians: A follow-up study. Photodermatol Photoimmunol Photomed 2014; 30(5): 231-6.
[] [PMID: 24118606]
Schnyder B, Pichler WJ. Mechanisms of drug-induced allergy. Mayo Clin Proc 2009; 84(3): 268-72.
[] [PMID: 19252115]
Yoshiki R, Kabashima K, Sugita K, Atarashi K, Shimauchi T, Tokura Y. IL-10-producing Langerhans cells and regulatory T cells are responsible for depressed contact hypersensitivity in grafted skin. J Invest Dermatol 2009; 129(3): 705-13.
[] [PMID: 18843293]
Tokura Y. Drug photoallergy. J Cutan Immunol Allergy 2018; 1(2): 48-57.
Sattler UGA, Mueller-Klieser W. The anti-oxidant capacity of tumour glycolysis. Int J Radiat Biol 2009; 85(11): 963-71.
[] [PMID: 19895273]
Frank J, Flaccus A, Schwarz C, Lambert C, Biesalski HK. Ascorbic acid suppresses cell death in rat DS-sarcoma cancer cells induced by 5-aminolevulinic acid-based photodynamic therapy. Free Radic Biol Med 2006; 40(5): 827-36.
[] [PMID: 16520235]
Goł Ğb J, Nowis D, Skrzycki M, et al. Antitumor effects of photodynamic therapy are potentiated by 2-methoxyestradiol. A superoxide dismutase inhibitor. J Biol Chem 2003; 278(1): 407-14.
[] [PMID: 12409296]
Hadjur C, Richard MJ, Parat MO, Jardon P, Favier A. Photodynamic effects of hypericin on lipid peroxidation and antioxidant status in melanoma cells. Photochem Photobiol 1996; 64(2): 375-81.
[] [PMID: 8760577]
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.
[] [PMID: 12659143]
Matroule JY, Bonizzi G, Morlière P, et al. Pyropheophorbide-a methyl ester-mediated photosensitization activates transcription factor NF-kappaB through the interleukin-1 receptor-dependent signaling pathway. J Biol Chem 1999; 274(5): 2988-3000.
[] [PMID: 9915837]
Wang HP, Hanlon JG, Rainbow AJ, Espiritu M, Singh G. Up-regulation of Hsp27 plays a role in the resistance of human colon carcinoma HT29 cells to photooxidative stress. Photochem Photobiol 2002; 76(1): 98-104.
[<0098:UROHPA>2.0.CO;2] [PMID: 12126313]
Hanlon JG, Adams K, Rainbow AJ, Gupta RS, Singh G. Induction of Hsp60 by photofrin-mediated photodynamic therapy. J Photochem Photobiol B 2001; 64(1): 55-61.
[] [PMID: 11705730]
Nonaka M, Ikeda H, Inokuchi T. Inhibitory effect of heat shock protein 70 on apoptosis induced by photodynamic therapy in vitro. Photochem Photobiol 2004; 79(1): 94-8.
[] [PMID: 14982037]
Szokalska A, Makowski M, Nowis D, et al. Proteasome inhibition potentiates antitumor effects of photodynamic therapy in mice through induction of endoplasmic reticulum stress and unfolded protein response. Cancer Res 2009; 69(10): 4235-43.
[] [PMID: 19435917]
Dolmans DEJGJ, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nat Rev Cancer 2003; 3(5): 380-7.
[] [PMID: 12724736]
Dougherty TJ, Gomer CJ, Henderson BW, et al. Photodynamic therapy. J Natl Cancer Inst 1998; 90(12): 889-905.
[] [PMID: 9637138]
McCaughan JS Jr. Photodynamic therapy. Drugs Aging 1999; 15(1): 49-68.
[] [PMID: 10459732]
Hamblin MR, Hasan T. Photodynamic therapy: A new antimicrobial approach to infectious disease? Photochem Photobiol Sci 2004; 3(5): 436-50.
[] [PMID: 15122361]
Jori G, Fabris C, Soncin M, et al. Photodynamic therapy in the treatment of microbial infections: Basic principles and perspective applications. Lasers Surg Med 2006; 38(5): 468-81.
[] [PMID: 16788934]
Pervaiz S, Olivo M. Art and science of photodynamic therapy. Clin Exp Pharmacol Physiol 2006; 33(5-6): 551-6.
[] [PMID: 16700893]
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.
[] [PMID: 11023333]
Castano AP, Demidova TN, Hamblin MR. Mechanisms in photodynamic therapy: Part one—photosensitizers, photochemistry and cellular localization. Photodiagn Photodyn Ther 2004; 1(4): 279-93.
[] [PMID: 25048432]
Niemz MH. Laser-tissue interactions Fundamentals and applications. Berlin, Heidelberg, New York: Springer 2007.
Prasad PN. Introduction to biophotonics. Hoboken: Wiley 2003.
Niemz MH. Laser-tissue interactions. Berlin: Springer 1996.
Anderson RR, Parrish JA. The optics of human skin. J Invest Dermatol 1981; 77(1): 13-9.
[] [PMID: 7252245]
Juzeniene A, Nielsen KP, Moan J. Biophysical aspects of photodynamic therapy. J Environ Pathol Toxicol Oncol 2006; 25(1-2): 7-28.
[] [PMID: 16566708]
Castelani A, Pace GP, Concioli M. Photodynamic effect of haematoporphyrin on blood microcirculation. J Pathol Bacteriol 1963; 86(1): 99-102.
[] [PMID: 14019186]
Star WM, Marijnissen HP, van den Berg-Blok AE, Versteeg JA, Franken KA, Reinhold HS. Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers. Cancer Res 1986; 46(5): 2532-40.
[PMID: 3697992]
Bhuvaneswari R, Gan YY, Soo KC, Olivo M. The effect of photodynamic therapy on tumor angiogenesis. Cell Mol Life Sci 2009; 66(14): 2275-83.
[] [PMID: 19333552]
Tseng MT, Reed MWR, Ackermann DM, Schuschke DA, Wieman TJ, Miller FN. Photodynamic therapy induced ultrastructural alterations in microvasculature of the rat cremaster muscle. Photochem Photobiol 1988; 48(5): 675-81.
[] [PMID: 2977226]
Henderson BW, Waldow SM, Mang TS, Potter WR, Malone PB, Dougherty TJ. Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy. Cancer Res 1985; 45(2): 572-6.
[PMID: 3967232]
Henderson BW, Fingar VH. Oxygen limitation of direct tumor cell kill during photodynamic treatment of a murine tumor model. Photochem Photobiol 1989; 49(3): 299-304.
[] [PMID: 2525260]
Gomer CJ, Rucker N, Murphree AL. Differential cell photosensitivity following porphyrin photodynamic therapy. Cancer Res 1988; 48(16): 4539-42.
[PMID: 2969280]
West CML, West DC, Kumar S, Moore JV. A comparison of the sensitivity to photodynamic treatment of endothelial and tumour cells in different proliferative states. Int J Radiat Biol 1990; 58(1): 145-56.
[] [PMID: 1973432]
Fingar VH, Wieman TJ, Wiehle SA, Cerrito PB. The role of microvascular damage in photodynamic therapy: the effect of treatment on vessel constriction, permeability, and leukocyte adhesion. Cancer Res 1992; 52(18): 4914-21.
[PMID: 1387584]
Chen B, Pogue BW, Luna JM, Hardman RL, Hoopes PJ, Hasan T. Tumor vascular permeabilization by vascular-targeting photosensitization: Effects, mechanism, and therapeutic implications. Clin Cancer Res 2006; 12(3): 917-23.
[] [PMID: 16467106]
Mitra S, Foster TH. In vivo confocal fluorescence imaging of the intratumor distribution of the photosensitizer mono-L-aspartylchlorin-e6. Neoplasia 2008; 10(5): 429-38.
[] [PMID: 18472960]
Snyder JW, Greco WR, Bellnier DA, Vaughan L, Henderson BW. Photodynamic therapy: A means to enhanced drug delivery to tumors. Cancer Res 2003; 63(23): 8126-31.
[PMID: 14678965]
Hirschberg H, Uzal FA, Chighvinadze D, Zhang MJ, Peng Q, Madsen SJ. Disruption of the blood-brain barrier following ALA-mediated photodynamic therapy. Lasers Surg Med 2008; 40(8): 535-42.
[] [PMID: 18798293]
Korbelik M, Cecic I. Contribution of myeloid and lymphoid host cells to the curative outcome of mouse sarcoma treatment by photodynamic therapy. Cancer Lett 1999; 137(1): 91-8.
[] [PMID: 10376798]
de Vree WJ, Essers MC, Koster JF, Sluiter W. Role of interleukin 1 and granulocyte colony-stimulating factor in photofrin-based photodynamic therapy of rat rhabdomyosarcoma tumors. Cancer Res 1997; 57(13): 2555-8.
[PMID: 9205052]
Kousis PC, Henderson BW, Maier PG, Gollnick SO. Photodynamic therapy enhancement of antitumor immunity is regulated by neutrophils. Cancer Res 2007; 67(21): 10501-10.
[] [PMID: 17974994]
Korbelik M, Cecic I. Mechanism of tumor destruction by photodynamic therapy. In: Handbook of photochemistry and photobiology. 2003.
Sun J, Cecic I, Parkins CS, Korbelik M. Neutrophils as inflammatory and immune effectors in photodynamic therapy-treated mouse SCCVII tumours. Photochem Photobiol Sci 2002; 1(9): 690-5.
[] [PMID: 12665307]
Mitra A, Stables GI. Topical photodynamic therapy for non-cancerous skin conditions. Photodiagn Photodyn Ther 2006; 3(2): 116-27.
[] [PMID: 25049103]
Juzeniene A, Moan J. The history of PDT in Norway. Photodiagn Photodyn Ther 2007; 4(1): 3-11.
[] [PMID: 25047184]
Castano AP, Demidova TN, Hamblin MR. Mechanisms in photodynamic therapy: Part three—Photosensitizer pharmacokinetics, biodistribution, tumor localization and modes of tumor destruction. Photodiagn Photodyn Ther 2005; 2(2): 91-106.
[] [PMID: 25048669]
Tímár J, Mészáros L, Ladányi A, Puskás LG, Rásó E. Melanoma genomics reveals signatures of sensitivity to bio- and targeted therapies. Cell Immunol 2006; 244(2): 154-7.
[] [PMID: 17433276]
Ketabchi A, MacRobert A, Speight PM, Bennett JH. Induction of apoptotic cell death by photodynamic therapy in human keratinocytes. Arch Oral Biol 1998; 43(2): 143-9.
[] [PMID: 9602293]
Nowis D, Stokłosa T, Legat M, Issat T, Jakóbisiak M, Gołąb J. The influence of photodynamic therapy on the immune response. Photodiagn Photodyn Ther 2005; 2(4): 283-98.
[] [PMID: 25048870]
Gorter A, Meri S. Immune evasion of tumor cells using membrane-bound complement regulatory proteins. Immunol Today 1999; 20(12): 576-82.
[] [PMID: 10562709]
Ochsner M. Light scattering of human skin: A comparison between zinc(II)— phthalocyanine and photofrin II®. J Photochem Photobiol B 1996; 32(1-2): 3-9.
[] [PMID: 8725049]
Saikali S, Avril T, Collet B, et al. Expression of nine tumour antigens in a series of human glioblastoma multiforme: Interest of EGFRvIII, IL-13Rα2, gp100 and TRP-2 for immunotherapy J Neurooncol 2006; 81(2): 139-48.
[] [PMID: 17004103]
Roland CL, Harken AH, Sarr MG, Barnett CC. Evidence-based surgical hypothesis: ICAM-1 expression determines malignant potential of cancer. J Surg 2007; 141(6): 705-7.
Agostinis P, Berg K, Cengel KA, et al. Photodynamic therapy of cancer: An update. CA Cancer J Clin 2011; 61: 250-81.
[] [PMID: 21617154]
Dandler J, Scheer H. Inhibition of aggregation of [Pd]-bacteriochlorophyllides in mesoporous silica. Langmuir 2009; 25(20): 11988-92.
[] [PMID: 19772311]
Hamblin MR, Newman EL. On the mechanism of the tumour-localising effect in photodynamic therapy. J Photochem Photobiol B 1994; 23(1): 3-8.
[] [PMID: 8021748]
Nakamura H, Jun F, Maeda H. Development of next-generation macromolecular drugs based on the EPR effect: Challenges and pitfalls. Expert Opin Drug Deliv 2015; 12(1): 705-7.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy