Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Photodynamic therapy for cancer


The therapeutic properties of light have been known for thousands of years, but it was only in the last century that photodynamic therapy (PDT) was developed. At present, PDT is being tested in the clinic for use in oncology — to treat cancers of the head and neck, brain, lung, pancreas, intraperitoneal cavity, breast, prostate and skin. How does PDT work, and how can it be used to treat cancer and other diseases?

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Mechanism of action of photodynamic therapy (PDT).
Figure 2: Type I and type II reaction in photodynamic therapy (PDT).
Figure 3: Localization of a photosensitizer to vascular endothelial cells.


  1. 1

    Daniell, M. D. & Hill, J. S. A history of photodynamic therapy. Aust. NZ J. Surg. 61, 340–348 (1991).

    CAS  Google Scholar 

  2. 2

    Ackroyd, R., Kelty, C., Brown, N. & Reed, M. The history of photodetection and photodynamic therapy. Photochem. Photobiol. 74, 656–669 (2001).

    CAS  PubMed  Google Scholar 

  3. 3

    Spikes, J. D. in Primary Photoprocesses in Biology and Medicine (eds Berghausen, R. V., Jori, G., Land, E. J. & Truscott, T. H.) 209–227 (Plenum Press, New York, 1985).

    Google Scholar 

  4. 4

    Finsen, N. R. Phototherapy (Edward Arnold, London, 1901).

    Google Scholar 

  5. 5

    Raab, O. Uber die Wirkung fluoreszierender Stoffe auf Infusorien. Zeitung Biol. 39, 524–526 (1900).

    CAS  Google Scholar 

  6. 6

    Prime, J. Les accidents toxiques par l'eosinate de sodium (Jouve and Boyer, Paris, 1900).

    Google Scholar 

  7. 7

    von Tappeiner, H. & Jesionek, A. Therapeutische versuche mit fluoreszierenden stoffen. Muench Med. Wochenschr. 47, 2042–2044 (1903).

    Google Scholar 

  8. 8

    von Tappeiner, H. & Jodlbauer, A. Die sensiblilisierende Wirkung fluoreszierender Substanzer Gesammte Untersuchungen uber die photodynamische Erscheinerung (Voger, F. C., Leipzig, 1907).

    Google Scholar 

  9. 9

    Epstein, J. H. Phototoxicity and photoallergy. Semin. Cutan. Med. Surg. 18, 274–284 (1999).

    CAS  PubMed  Google Scholar 

  10. 10

    Epstein, J. H. Phototherapy and photochemotherapy. N. Engl. J. Med. 322, 1149–1151 (1990).

    CAS  PubMed  Google Scholar 

  11. 11

    Hausmann, W. Die sensiblisierende Wirkung des Hematoporphyrins. Biochem. Zeitung 30, 276–316 (1911).

    CAS  Google Scholar 

  12. 12

    Meyer-Betz, F. Untersuchungen uber die biologische photodynamische Wirkung des Hematoporphyrins und anderer Derivative des Blut und Galenafarbstoffs. Dtsch Arch. Klin. 112, 476–503 (1913).

    Google Scholar 

  13. 13

    Lipson, R. L. & Baldes, E. J. The photodynamic properties of a particular hematoporphyrin derivative. Arch. Dermatol. 82, 508–516 (1960).

    CAS  PubMed  Google Scholar 

  14. 14

    Lipson, R. L., Baldes, E. J. & Olsen, A. M. The use of an derivative of hematoporphyrin in tumor detection. J. Natl Cancer Inst. 26, 1–11 (1961).

    CAS  PubMed  Google Scholar 

  15. 15

    Schwartz, S. K., Abolon, K. & Vermund, H. Some relationships of porphyrins, X-rays and tumors. Univ. Minn. Med. Bull. 27, 7–8 (1955).

    Google Scholar 

  16. 16

    Lipson, R. L., Baldes, E. J. & Olsen, A. M. Hematoporphyrin derivative: a new aid for endoscopic detection of malignant disease. J. Thorac. Cardiovasc. Surg. 42, 623–629 (1961).

    CAS  PubMed  Google Scholar 

  17. 17

    Dougherty, T. et al. Photodynamic therapy. JNCI Cancer Spectrum 90, 889–905 (1998).

    CAS  Google Scholar 

  18. 18

    Hasan, T., Ortel, B., Moor, A. & Pogue, B. in Holland–Frei Cancer Medicine (eds Kufe, D. et al.) Ch. 40 (BC Decker, Inc., Hamilton, Ontario, 2003).

    Google Scholar 

  19. 19

    Diamond, I. et al. Photodynamic therapy of malignant tumours. Lancet 2, 1175–1177 (1972).

    CAS  PubMed  Google Scholar 

  20. 20

    Dougherty, T. J., Grindey, G. B., Fiel, R., Weishaupt, K. R. & Boyle, D. G. Photoradiation therapy. II. Cure of animal tumors with hematoporphyrin and light. J. Natl Cancer Inst. 55, 115–121 (1975).

    CAS  PubMed  Google Scholar 

  21. 21

    Kelly, J. F., Snell, M. E. & Berenbaum, M. C. Photodynamic destruction of human bladder carcinoma. Br. J. Cancer 31, 237–244 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Kelly, J. F. & Snell, M. E. Hematoporphyrin derivative: a possible aid in the diagnosis and therapy of carcinoma of the bladder. J. Urol. 115, 150–151 (1976).

    CAS  PubMed  Google Scholar 

  23. 23

    Dougherty, T. J. et al. Photoradiation therapy for the treatment of malignant tumors. Cancer Res. 38, 2628–2635 (1978).

    CAS  PubMed  Google Scholar 

  24. 24

    Hayata, Y., Kato, H., Konaka, C., Ono, J. & Takizawa, N. Hematoporphyrin derivative and laser photoradiation in the treatment of lung cancer. Chest 81, 269–277 (1982).

    CAS  PubMed  Google Scholar 

  25. 25

    McCaughan, J. S. Jr, Hicks, W., Laufman, L., May, E. & Roach, R. Palliation of esophageal malignancy with photoradiation therapy. Cancer 54, 2905–2910 (1984).

    PubMed  Google Scholar 

  26. 26

    Balchum, O. J., Doiron, D. R. & Huth, G. C. Photoradiation therapy of endobronchial lung cancers employing the photodynamic action of hematoporphyrin derivative. Lasers Surg. Med. 4, 13–30 (1984).

    CAS  PubMed  Google Scholar 

  27. 27

    Hayata, Y., Kato, H., Okitsu, H., Kawaguchi, M. & Konaka, C. Photodynamic therapy with hematoporphyrin derivative in cancer of the upper gastrointestinal tract. Semin. Surg. Oncol. 1, 1–11 (1985).

    CAS  PubMed  Google Scholar 

  28. 28

    Dougherty, T. J. et al. Photoradiation in the treatment of recurrent breast carcinoma. J. Natl Cancer Inst. 62, 231–237 (1979).

    CAS  PubMed  Google Scholar 

  29. 29

    Mang, T. S., Allison, R., Hewson, G., Snyder, W. & Moskowitz, R. A Phase II/III study of tin ethyl etiopurpurin (Purlytin)-induced photodynamic therapy for the treatment of recurrent cutaneous metastatic breast cancer. Cancer J. Sci. Am. 4, 378–384 (1998).

    CAS  PubMed  Google Scholar 

  30. 30

    Dimofte, A., Zhu, T. C., Hahn, S. M. & Lustig, R. A. In vivo light dosimetry for motexafin lutetium-mediated PDT of breast cancer. Lasers Surg. Med. 31, 305–312 (2002).

    PubMed  Google Scholar 

  31. 31

    Ward, B. G., Forbes, I. J., Cowled, P. A., McEvoy, M. M. & Cox, L. W. The treatment of vaginal recurrences of gynecologic malignancy with phototherapy following hematoporphyrin derivative pretreatment. Am. J. Obstet. Gynecol. 142, 356–357 (1982).

    CAS  PubMed  Google Scholar 

  32. 32

    Hornung, R. Photomedical approaches for the diagnosis and treatment of gynecologic cancers. Curr. Drug Targets Immune Endocr. Metabol. Disord. 1, 165–177 (2001).

    CAS  PubMed  Google Scholar 

  33. 33

    Fehr, M. K. et al. Photodynamic therapy of vulvar intraepithelial neoplasia III using topically applied 5-aminolevulinic acid. Gynecol. Oncol. 84, 62–66 (2002).

    Google Scholar 

  34. 34

    Gomer, C. J., Doiron, D. R., Jester, J. V., Szirth, B. C. & Murphree, A. L. Hematoporphyrin derivative photoradiation therapy for the treatment of intraocular tumors: examination of acute normal ocular tissue toxicity. Cancer Res. 43, 721–727 (1983).

    CAS  PubMed  Google Scholar 

  35. 35

    Favilla, I. et al. Photodynamic therapy: a 5 year study of its effectiveness in the treatment of posterior uveal melanoma, and evaluation of haematoporphyrin uptake and photocytotoxicity of melanoma cells in tissue culture. Melanoma Res. 5, 355–364 (1995).

    CAS  PubMed  Google Scholar 

  36. 36

    Landau, I. M., Steen, B. & Seregard, S. Photodynamic therapy for circumscribed choroidal haemangioma. Acta Ophthalmol. Scand. 80, 531–536 (2002).

    PubMed  Google Scholar 

  37. 37

    Sandeman, D. R. Photodynamic therapy in the management of malignant gliomas: a review. Lasers Med. Sci. 1, 163–167 (1986).

    Google Scholar 

  38. 38

    Hill, J. S. et al. Selective uptake of hematoporphyrin derivative into human cerebral glioma. Neurosurgery 26, 248–254 (1990).

    CAS  PubMed  Google Scholar 

  39. 39

    Popovic, E. A., Kaye, A. H. & Hill, J. S. Photodynamic therapy of brain tumors. J. Clin. Laser Med. Surg. 14, 251–261 (1996).

    CAS  PubMed  Google Scholar 

  40. 40

    Rosenthal, M. A. et al. Phase I and pharmacokinetic study of photodynamic therapy for high-grade gliomas using a novel boronated porphyrin. J. Clin. Oncol. 19, 519–524 (2001).

    CAS  PubMed  Google Scholar 

  41. 41

    Schweitzer, V. G. Photodynamic therapy for treatment of head and neck cancer. Otolaryngol. Head Neck Surg. 102, 225–232 (1990).

    CAS  PubMed  Google Scholar 

  42. 42

    Biel, M. A. Photodynamic therapy and the treatment of head and neck neoplasia. Laryngoscope 108, 1259–1268 (1998).

    CAS  PubMed  Google Scholar 

  43. 43

    Barr, H., Krasner, N., Boulos, P. B., Chatlani, P. & Bown, S. G. Photodynamic therapy for colorectal cancer: a quantitative pilot study. Br. J. Surg. 77, 93–96 (1990).

    CAS  PubMed  Google Scholar 

  44. 44

    Mlkvy, P. et al. Photodynamic therapy for gastrointestinal tumors using three photosensitizers — ALA induced PPIX, Photofrin and MTHPC. A pilot study. Neoplasma 45, 157–161 (1998).

    CAS  PubMed  Google Scholar 

  45. 45

    Allison, R. R., Mang, T. S. & Wilson, B. D. Photodynamic therapy for the treatment of nonmelanomatous cutaneous malignancies. Semin. Cutan. Med. Surg. 17, 153–163 (1998).

    CAS  PubMed  Google Scholar 

  46. 46

    Taber, S. W., Fingar, V. H., Coots, C. T. & Wieman, T. J. Photodynamic therapy using mono-L-aspartyl chlorin e6 (Npe6) for the treatment of cutaneous disease: a Phase I clinical study. Clin. Cancer Res. 4, 2741–2746 (1998).

    CAS  PubMed  Google Scholar 

  47. 47

    DeLaney, T. F. et al. Phase I study of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors. Int. J. Radiat. Oncol. Biol. Phys. 25, 445–457 (1993).

    CAS  PubMed  Google Scholar 

  48. 48

    Pass, H. I. et al. Intrapleural photodynamic therapy: results of a phase I trial. Ann. Surg. Oncol. 1, 28–37 (1994).

    CAS  PubMed  Google Scholar 

  49. 49

    Ortner, M. A. et al. Photodynamic therapy of nonresectable cholangiocarcinoma. Gastroenterology 114, 536–542 (1998).

    CAS  PubMed  Google Scholar 

  50. 50

    Bown, S. G. et al. Photodynamic therapy for cancer of the pancreas. Gut 50, 549–557 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51

    McBride, G. Studies expand potential uses of photodynamic therapy. JNCI Cancer Spectrum 94, 1740–1742 (2002).

    Google Scholar 

  52. 52

    Henderson, B. W. & Dougherty, T. J. How does photodynamic therapy work? Photochem. Photobiol. 55, 145–157 (1992).

    CAS  PubMed  Google Scholar 

  53. 53

    Gomer, C. J. & Razum, N. J. Acute skin response in albino mice following porphyrin photosensitization under oxic and anoxic conditions. Photochem. Photobiol. 40, 435–439 (1984).

    CAS  PubMed  Google Scholar 

  54. 54

    Moan, J. & Berg, K. The photodegradation of porphyrins in cells can be used to estimate the lifetime of singlet oxygen. Photochem. Photobiol. 53, 549–553 (1991).

    CAS  PubMed  Google Scholar 

  55. 55

    Henderson, B. W. et al. Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy. Cancer Res. 45, 572–576 (1985).

    CAS  PubMed  Google Scholar 

  56. 56

    Korbelik, M. & Krosl, G. Cellular levels of photosensitisers in tumours: the role of proximity to the blood supply. Br. J. Cancer 70, 604–610 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57

    Tromberg, B. J. et al. In vivo tumor oxygen tension measurements for the evaluation of the efficiency of photodynamic therapy. Photochem. Photobiol. 52, 375–385 (1990).

    CAS  PubMed  Google Scholar 

  58. 58

    Pogue, B. W., Braun, R. D., Lanzen, J. L., Erickson, C. & Dewhirst, M. W. Analysis of the heterogeneity of pO2 dynamics during photodynamic therapy with verteporfin. Photochem. Photobiol. 74, 700–706 (2001).

    CAS  PubMed  Google Scholar 

  59. 59

    Pogue, B. W. et al. Photodynamic therapy with verteporfin in the radiation-induced fibrosarcoma-1 tumor causes enhanced radiation sensitivity. Cancer Res. 63, 1025–1033 (2003).

    CAS  PubMed  Google Scholar 

  60. 60

    Messmann, H. et al. Enhancement of photodynamic therapy with 5-aminolaevulinic acid-induced porphyrin photosensitisation in normal rat colon by threshold and light fractionation studies. Br. J. Cancer 72, 589–594 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    Pogue, B. W. & Hasan, T. A theoretical study of light fractionation and dose-rate effects in photodynamic therapy. Radiat. Res. 147, 551–559 (1997).

    CAS  PubMed  Google Scholar 

  62. 62

    Iinuma, S. et al. In vivo fluence rate and fractionation effects on tumor response and photobleaching: photodynamic therapy with two photosensitizers in an orthotopic rat tumor model. Cancer Res. 59, 6164–6170 (1999).

    CAS  PubMed  Google Scholar 

  63. 63

    Carmeliet, P. & Jain, R. K. Angiogenesis in cancer and other diseases: from genes to function to therapy. Nature 407, 249–257 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64

    Jain, R. K. & Carmeliet, P. F. Vessels of death or life. Sci. Am. 285, 38–45 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65

    Star, W. M. et al. Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers. Cancer Res. 46, 2532–2540 (1986).

    CAS  PubMed  Google Scholar 

  66. 66

    Fingar, V. H., Wieman, T. J. & Haydon, P. S. The effects of thrombocytopenia on vessel stasis and macromolecular leakage after photodynamic therapy using photofrin. Photochem. Photobiol. 66, 513–517 (1997).

    CAS  PubMed  Google Scholar 

  67. 67

    Fingar, V. H. et al. Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD). Br. J. Cancer 79, 1702–1708 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68

    Dolmans, D. E. et al. Vascular accumulation of a novel photosensitizer, MV6401, causes selective thrombosis in tumor vessels after photodynamic therapy. Cancer Res. 62, 2151–2156 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. 69

    Henderson, B. W. & Fingar, V. H. Relationship of tumor hypoxia and response to photodynamic treatment in an experimental mouse tumor. Cancer Res. 47, 3110–3114 (1987).

    CAS  PubMed  Google Scholar 

  70. 70

    Chen, Q., Chen, H. & Hetzel, F. W. Tumor oxygenation changes post-photodynamic therapy. Photochem. Photobiol. 63, 128–131 (1996).

    CAS  PubMed  Google Scholar 

  71. 71

    Busch, T. M. et al. Photodynamic therapy creates fluence rate-dependent gradients in the intratumoral spatial distribution of oxygen. Cancer Res. 62, 7273–7279 (2002).

    CAS  PubMed  Google Scholar 

  72. 72

    Henderson, B. W. & Fingar, V. H. Oxygen limitation of direct tumor cell kill during photodynamic treatment of a murine tumor model. Photochem. Photobiol. 49, 299–304 (1989).

    CAS  PubMed  Google Scholar 

  73. 73

    Ferrario, A. et al. Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma. Cancer Res. 60, 4066–4069 (2000).

    CAS  PubMed  Google Scholar 

  74. 74

    Ferrario, A., von Tiehl, K., Wong, S., Luna, M. & Gomer, C. J. Cyclooxygenase-2 inhibitor treatment enhances photodynamic therapy-mediated tumor response. Cancer Res. 62, 3956–3961 (2002).

    CAS  PubMed  Google Scholar 

  75. 75

    Reference deleted in proof.

  76. 76

    Shumaker, B. P. & Hetzel, F. W. Clinical laser photodynamic therapy in the treatment of bladder carcinoma. Photochem. Photobiol. 46, 899–901 (1987).

    CAS  PubMed  Google Scholar 

  77. 77

    Gollnick, S. O., Liu, X., Owczarczak, B., Musser, D. A. & Henderson, B. W. Altered expression of interleukin 6 and interleukin 10 as a result of photodynamic therapy in vivo. Cancer Res. 57, 3904–3909 (1997).

    CAS  PubMed  Google Scholar 

  78. 78

    de Vree, W. J. et al. Evidence for an important role of neutrophils in the efficacy of photodynamic therapy in vivo. Cancer Res. 56, 2908–2911 (1996).

    CAS  PubMed  Google Scholar 

  79. 79

    Korbelik, M., Krosl, G., Krosl, J. & Dougherty, G. J. The role of host lymphoid populations in the response of mouse EMT6 tumor to photodynamic therapy. Cancer Res. 56, 5647–5652 (1996).

    CAS  PubMed  Google Scholar 

  80. 80

    Korbelik, M. & Dougherty, G. J. Photodynamic therapy-mediated immune response against subcutaneous mouse tumors. Cancer Res. 59, 1941–1946 (1999).

    CAS  PubMed  Google Scholar 

  81. 81

    Gollnick, S. O., Vaughan, L. & Henderson, B. W. Generation of effective antitumor vaccines using photodynamic therapy. Cancer Res. 62, 1604–1608 (2002).

    CAS  PubMed  Google Scholar 

  82. 82

    Jain, R. K. Delivery of molecular and cellular medicine to solid tumors. Adv. Drug Deliv. Rev. 46, 149–168 (2001).

    CAS  PubMed  Google Scholar 

  83. 83

    Jain, R. K. The next frontier of molecular medicine: delivery of therapeutics. Nature Med. 4, 655–657 (1998).

    CAS  PubMed  Google Scholar 

  84. 84

    Dolmans, D. E. et al. Targeting tumor vasculature and cancer cells in orthotopic breast tumor by fractionated photosensitizer dosing photodynamic therapy. Cancer Res. 62, 4289–4294 (2002).

    CAS  PubMed  Google Scholar 

  85. 85

    Dougherty, T. J. An update on photodynamic therapy applications. J. Clin. Laser Med. Surg. 20, 3–7 (2002).

    PubMed  PubMed Central  Google Scholar 

  86. 86

    Cramers, P. et al. Foscan uptake and tissue distribution in relation to photodynamic efficacy. Br. J. Cancer 88, 283–290 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. 87

    Ruoslahti, E. Specialization of tumour vasculature. Nature Rev. Cancer 2, 83–90 (2002).

    Google Scholar 

  88. 88

    Peng, Q., Moan, J. & Nesland, J. M. Correlation of subcellular and intratumoral photosensitizer localization with ultrastructural features after photodynamic therapy. Ultrastruct. Pathol. 20, 109–129 (1996).

    CAS  PubMed  Google Scholar 

  89. 89

    Bachor, R., Shea, C., Gillies, R. & Hasan, T. Photosensitized destruction of human bladder carcinoma cells treated with chlorin e6-conjugated microspheres. Proc. Natl Acad. Sci. USA 88, 1580–1584 (1991).

    CAS  PubMed  Google Scholar 

  90. 90

    Duska, L. R., Hamblin, M. R., Miller, J. L. & Hasan, T. Combination photoimmunotherapy and cisplatin: effects on human ovarian cancer ex vivo. JNCI Cancer Spectrum 91, 1557–1563 (1999).

    CAS  Google Scholar 

  91. 91

    Dougherty, T. J. Hematoporphyrin as a photosensitizer of tumors. Photochem. Photobiol. 38, 377–379 (1983).

    CAS  PubMed  Google Scholar 

  92. 92

    Dougherty, T. J., Potter, W. R. & Weishaupt, K. R. The structure of the active component of hematoporphyrin derivative. Prog. Clin. Biol. Res. 170, 301–314 (1984).

    CAS  PubMed  Google Scholar 

  93. 93

    Orenstein, A. et al. A comparative study of tissue distribution and photodynamic therapy selectivity of chlorin e6, Photofrin II and ALA-induced protoporphyrin IX in a colon carcinoma model. Br. J. Cancer 73, 937–944 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 94

    Sibata, C. H., Colussi, V. C., Oleinick, N. L. & Kinsella, T. J. Photodynamic therapy in oncology. Expert Opin. Pharmacother. 2, 917–927 (2001).

    CAS  PubMed  Google Scholar 

  95. 95

    Ris, H. B. et al. Photodynamic therapy with chlorins for diffuse malignant mesothelioma: initial clinical results. Br. J. Cancer 64, 1116–1120 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. 96

    Grosjean, P., Savary, J. & Wagnieres, G. Tetra (m-hyrophenyl) chlorin clinical photodynamic therapy of early bronchial and esophageal cancers. Lasers Med. Sci. 8, 235–243 (1993).

    Google Scholar 

  97. 97

    Rassmussan-Taxdal, D. S., Ward, G. E. & Figge, F. H. Fluorescence of human lymphatic and cancer tissues following high doses of intravenous hematoporphyrin. Cancer 8, 78–81 (1955).

    Google Scholar 

  98. 98

    Braichotte, D. R., Wagnieres, G. A., Bays, R., Monnier, P. & van den Bergh, H. E. Clinical pharmacokinetic studies of photofrin by fluorescence spectroscopy in the oral cavity, the esophagus, and the bronchi. Cancer 75, 2768–2778 (1995).

    CAS  PubMed  Google Scholar 

  99. 99

    Kennedy, J. C., Pottier, R. H. & Pross, D. C. Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J. Photochem. Photobiol. B 6, 143–148 (1990).

    CAS  PubMed  Google Scholar 

  100. 100

    Kennedy, J. C., Marcus, S. L. & Pottier, R. H. Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): mechanisms and clinical results. J. Clin. Laser Med. Surg. 14, 289–304 (1996).

    CAS  PubMed  Google Scholar 

  101. 101

    Peng, Q. et al. 5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges. Cancer 79, 2282–2308 (1997).

    CAS  PubMed  Google Scholar 

  102. 102

    Stummer, W. et al. Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. J. Neurosurg. 93, 1003–1013 (2000).

    CAS  PubMed  Google Scholar 

  103. 103

    Schmidt-Erfurth, U. & Hasan, T. Mechanisms of action of photodynamic therapy with verteporfin for the treatment of age-related macular degeneration. Surv. Ophthalmol. 45, 195–214 (2000).

    CAS  PubMed  Google Scholar 

  104. 104

    Endlicher, E. et al. Endoscopic fluorescence detection of low and high grade dysplasia in Barrett's oesophagus using systemic or local 5-aminolaevulinic acid sensitisation. Gut 48, 314–319 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. 105

    Berg, K. et al. Photochemical internalization: a novel technology for delivery of macromolecules into cytosol. Cancer Res. 59, 1180–1183 (1999).

    CAS  PubMed  Google Scholar 

  106. 106

    Mittra, R. A. & Singerman, L. J. Recent advances in the management of age-related macular degeneration. Optom. Vis. Sci. 79, 218–224 (2002).

    PubMed  Google Scholar 

  107. 107

    Photodynamic therapy with verteporfin for age-related macular degeneration. American Academy of Ophthalmology. Ophthalmology 107, 2314–2317 (2000).

  108. 108

    Ortu, P., LaMuraglia, G. M., Roberts, W. G., Flotte, T. J. & Hasan, T. Photodynamic therapy of arteries. A novel approach for treatment of experimental intimal hyperplasia. Circulation 85, 1189–1196 (1992).

    CAS  PubMed  Google Scholar 

  109. 109

    Chou, T. M. et al. Photodynamic therapy: applications in atherosclerotic vascular disease with motexafin lutetium. Catheter Cardiovasc. Interv. 57, 387–394 (2002).

    PubMed  Google Scholar 

  110. 110

    Szeimies, R. M., Landthaler, M. & Karrer, S. Non-oncologic indications for ALA-PDT. J. Dermatolog. Treat. 13 (Suppl. 1), S13–S18 (2002).

    CAS  PubMed  Google Scholar 

  111. 111

    Leman, J. A. & Morton, C. A. Photodynamic therapy: applications in dermatology. Expert Opin. Biol. Ther. 2, 45–53 (2002).

    CAS  PubMed  Google Scholar 

  112. 112

    Trauner, K. B. et al. Photodynamic synovectomy using benzoporphyrin derivative in an antigen-induced arthritis model for rheumatoid arthritis. Photochem. Photobiol. 67, 133–139 (1998).

    CAS  PubMed  Google Scholar 

  113. 113

    Soukos, N. S., Ximenez-Fyvie, L. A., Hamblin, M. R., Socranski, S. S. & Hasan, T. Targeted antimicrobial photochemotherapy. Antimicrob. Agents Chemother. 42, 2595–2601 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. 114

    Hamblin, M. R., Zahra, T., Contag, C. H., McManus, A. T. & Hasan, T. Optical monitoring and treatment of potentially lethal wound infections in vivo. J. Infect. Dis. (in the press).

  115. 115

    Hamblin, M. R., Miller, J. L. & Hasan, T. Effect of charge on the interaction of site-specific photoimmunoconjugates with human ovarian cancer cells. Cancer Res. 56, 5205–5210 (1996).

    CAS  PubMed  Google Scholar 

  116. 116

    Birchler, M., Viti, F., Zardi, L., Spiess, B. & Neri, D. Selective targeting and photocoagulation of ocular angiogenesis mediated by a phage-derived human antibody fragment. Nature Biotechnol. 17, 984–988 (1999).

    CAS  Google Scholar 

  117. 117

    Friedrich, S. W. et al. Antibody-directed effector cell therapy of tumors: analysis and optimization using a physiologically based pharmacokinetic model. Neoplasia 4, 449–463 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. 118

    de Bruijn, H. S., van der Veen, N., Robinson, D. J. & Star, W. M. Improvement of systemic 5-aminolevulinic acid-based photodynamic therapy in vivo using light fractionation with a 75-minute interval. Cancer Res. 59, 901–904 (1999).

    CAS  PubMed  Google Scholar 

  119. 119

    Mew, D., Wat, C. K., Towers, G. H. & Levy, J. G. Photoimmunotherapy: treatment of animal tumors with tumor-specific monoclonal antibody-hematoporphyrin conjugates. J. Immunol. 130, 1473–1477 (1983).

    CAS  PubMed  Google Scholar 

  120. 120

    Goff, B. A., Bamberg, M. & Hasan, T. Photoimmunotherapy of human ovarian carcinoma cells ex vivo. Cancer Res. 51, 4762–4767 (1991).

    CAS  PubMed  Google Scholar 

  121. 121

    Vrouenraets, M. B. et al. Development of meta-tetrahydroxyphenylchlorin-monoclonal antibody conjugates for photoimmunotherapy. Cancer Res. 59, 1505–1513 (1999).

    CAS  PubMed  Google Scholar 

  122. 122

    Allison, B. A., Pritchard, P. H. & Levy, J. G. Evidence for low-density lipoprotein receptor-mediated uptake of benzoporphyrin derivative. Br. J. Cancer 69, 833–839 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. 123

    Konan, Y. N., Gurny, R. & Allemann, E. State of the art in the delivery of photosensitizers for photodynamic therapy. J. Photochem. Photobiol. B 66, 89–106 (2002).

    CAS  PubMed  Google Scholar 

  124. 124

    Polo, L., Valduga, G., Jori, G. & Reddi, E. Low-density lipoprotein receptors in the uptake of tumour photosensitizers by human and rat transformed fibroblasts. Int. J. Biochem. Cell Biol. 34, 10–23 (2002).

    CAS  PubMed  Google Scholar 

  125. 125

    Dougherty, T. J. et al. The role of the peripheral benzodiazepine receptor in photodynamic activity of certain pyropheophorbide ether photosensitizers: albumin site II as a surrogate marker for activity. Photochem. Photobiol. 76, 91–97 (2002).

    CAS  PubMed  Google Scholar 

  126. 126

    Swamy, N., James, D. A., Mohr, S. C., Hanson, R. N. & Ray, R. An estradiol-porphyrin conjugate selectively localizes into estrogen receptor-positive breast cancer cells. Bioorg. Med. Chem. 10, 3237–3243 (2002).

    CAS  PubMed  Google Scholar 

  127. 127

    Zhou, C. N., Milanesi, C. & Jori, G. An ultrastructural comparative evaluation of tumors photosensitized by porphyrins administered in aqueous solution, bound to liposomes or to lipoproteins. Photochem. Photobiol. 48, 487–492 (1988).

    CAS  PubMed  Google Scholar 

  128. 128

    Richter, A. M. et al. Liposomal delivery of a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD), to tumor tissue in a mouse tumor model. Photochem. Photobiol. 57, 1000–1006 (1993).

    CAS  PubMed  Google Scholar 

Download references


We thank R. Anderson, T. Hasan and J. S. Hill for their critical and constructive comments, and A. C. Moor for her input on various sensitizers.

Author information



Corresponding authors

Correspondence to Dai Fukumura or Rakesh K. Jain.

Related links

Related links


bladder cancer

brain tumours

breast cancer

cervical cancer

colorectal cancer

gastric carcinoma

head and neck tumours

intraocular tumours

lung cancer


oesophageal cancer

pancreatic cancer

skin cancer










Inflammation of the skin.


The first photosensitizer used in photodynamic therapy by von Tappeiner.


The radiant energy incident per second across a sectional area of irradiated spot (power per unit area of light given in watts per square meter, W/m2; 1 W = 1 J/s).


The total energy of exposed light across a sectional area of irradiated spot (energy per unit area of exposed light, in joules per square meter, J/m2). The energy content of light is proportional to the wavelength of absorption.


The reaction of cells to a chemical reagent (or photosensitizer), light and oxygen.


A chemical that is required for photodynamic action. A photosensitizer transfers energy from the light to generate reactive oxygen species. Photofrin is the most widely used photosensitizer so far.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Dolmans, D., Fukumura, D. & Jain, R. Photodynamic therapy for cancer. Nat Rev Cancer 3, 380–387 (2003).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing