Abstract
Photo-induced reactions have the potential to revolutionize the fields of photomedicine and intelligent drug delivery by providing means of specifically inducing a chemical transformation in biological environments. The molecule that absorbs light and engages in photo-induced reactions is called the photosensitizer, and is the key component in this process. It transforms photon energy into a variety of reactions, such as photosensitized oxidations in photodynamic therapy (PDT) and ligand exchange in photoactivated chemotherapy (PACT). Ruthenium complexes, in particular, offer the possibility to maximize and fine-tune each of these reactions by changing the electronic properties, hydrophobicity, and steric hindrance of the ligands, thus affecting the energy and reactivity of the excited states. The field has advanced immensely in the last decade and we aim here to report on major achievements of ruthenium compounds for phototherapy. We will also discuss the mechanism of light-induced toxicity, the potential of upconverting systems for the activation of this type of drugs, as well as initial steps towards commercial applications of ruthenium complexes as PDT agents.
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Kasper, S., Rogers, S.L., Yancey, A.L., Schulz, P.M., Skwerer, R.G., Rosenthal, N.E.: Phototherapy in subsyndromal seasonal affective disorder (S-SAD) and “diagnosed” controls. Pharmacopsychiatry. 21(06), 428–429 (1988)
Maisels, M.J., McDonagh, A.F.: Phototherapy for neonatal jaundice. N. Engl. J. Med. 358(9), 920–928 (2008)
Zhang, P., Wu, M.X.: A clinical review of phototherapy for psoriasis. Lasers Med. Sci. 33(1), 173–180 (2018)
Bonnet, S.: Why develop photoactivated chemotherapy? Dalton Trans. 47(31), 10330–10343 (2018)
Velema, W.A., Szymanski, W., Feringa, B.L.: Photopharmacology: beyond proof of principle. J. Am. Chem. Soc. 136(6), 2178–2191 (2014)
Farrer, N.J., Salassa, L., Sadler, P.J.: Photoactivated chemotherapy (PACT): the potential of excited-state d-block metals in medicine. Dalton Trans. 38(48), 10690–10701 (2009)
Gai, S., Yang, G., Yang, P., He, F., Lin, J., Jin, D., Xing, B.: Recent advances in functional nanomaterials for light–triggered cancer therapy. Nano Today. 19, 146–187 (2018)
Mari, C., Pierroz, V., Ferrari, S., Gasser, G.: Combination of Ru(ii) complexes and light: new frontiers in cancer therapy. Chem. Sci. 6(5), 2660–2686 (2015)
Torre, L.A., Siegel, R.L., Ward, E.M., Jemal, A.: Global cancer incidence and mortality rates and trends—an update. Cancer Epidemiol. Biomark. Prev. 25(1), 16–27 (2016)
Jaque, D., Martínez Maestro, L., del Rosal, B., Haro-Gonzalez, P., Benayas, A., Plaza, J.L., Martín Rodríguez, E., García Solé, J.: Nanoparticles for photothermal therapies. Nanoscale. 6(16), 9494–9530 (2014)
Castano, A.P., Demidova, T.N., Hamblin, M.R.: Mechanisms in photodynamic therapy: part one—photosensitizers, photochemistry and cellular localization. Photodiagn. Photodyn. Ther. 1(4), 279–293 (2004)
Josefsen, L.B., Boyle, R.W.: Photodynamic therapy and the development of metal-based photosensitisers. Metal-Based Drugs. 2008, 276109 (2008)
Bacellar, I.O.L., Oliveira, M.C., Dantas, L.S., Costa, E.B., Junqueira, H.C., Martins, W.K., Durantini, A.M., Cosa, G., Di Mascio, P., Wainwright, M., Miotto, R., Cordeiro, R.M., Miyamoto, S., Baptista, M.S.: Photosensitized membrane permeabilization requires contact-dependent reactions between photosensitizer and lipids. J. Am. Chem. Soc. 140(30), 9606–9615 (2018)
Raab, O.: Uber die wirkung Fluorescirender Stoffe auf Infusorien. Z. Biol. 39, 524–546 (1900)
Jesionek, A., von Tappenier, H.: Zur behandlung der hautcarcinomit mit fluorescierenden stoffen. Münchener medizinische Wochenschrift. 50, 2042–2044 (1903)
Ackroyd, R., Kelty, C., Brown, N., Reed, M.: The history of photodetection and photodynamic therapy. Photochem. Photobiol. 74(5), 656–669 (2001)
Sies, H.: Oxidative stress: a concept in redox biology and medicine. Redox Biol. 4, 180–183 (2015)
Halliwell, B., Gutteridge, J.M.: Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem. J. 219(1), 1–14 (1984)
Tonolli, P.N., Chiarelli-Neto, O., Santacruz-Perez, C., Junqueira, H.C., Watanabe, I.-S., Ravagnani, F.G., Martins, W.K., Baptista, M.S.: Lipofuscin generated by UVA turns keratinocytes photosensitive to visible light. J. Invest. Dermatol. 137(11), 2447–2450 (2017)
Moan, J., Juzenas, P.: Singlet oxygen in photosensitization. J. Environ. Pathol. Toxicol. Oncol. 25(1–2), 29–50 (2006)
Dougherty, T.J., Gomer, C.J., Henderson, B.W., Jori, G., Kessel, D., Korbelik, M., Moan, J., Peng, Q.: Photodynamic therapy. J. Natl. Cancer Inst. 90(12), 889–905 (1998)
Spikes, J.D.: Chlorins as photosensitizers in biology and medicine. J. Photoch. Photobio. B. 6(3), 259–274 (1990)
Sternberg, E.D., Dolphin, D.: Second generation photodynamic agents: a review. J. Clin. Laser Med. Surg. 11(5), 233–241 (1993)
Kou, J., Dou, D., Yang, L.: Porphyrin photosensitizers in photodynamic therapy and its applications. Oncotarget. 8(46), 81591–81603 (2017)
Heinemann, F., Karges, J., Gasser, G.: Critical overview of the use of Ru(II) polypyridyl complexes as photosensitizers in one-photon and two-photon photodynamic therapy. Acc. Chem. Res. 50(11), 2727–2736 (2017)
Doherty, R.E., Sazanovich, I.V., McKenzie, L.K., Stasheuski, A.S., Coyle, R., Baggaley, E., Bottomley, S., Weinstein, J.A., Bryant, H.E.: Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand. Sci. Rep. 6(1), 22668 (2016)
Lazic, S., Kaspler, P., Shi, G., Monro, S., Sainuddin, T., Forward, S., Kasimova, K., Hennigar, R., Mandel, A., McFarland, S., Lilge, L.: Novel osmium-based coordination complexes as photosensitizers for panchromatic photodynamic therapy. Photochem. Photobiol. 93(5), 1248–1258 (2017)
Mari, C., Pierroz, V., Rubbiani, R., Patra, M., Hess, J., Spingler, B., Oehninger, L., Schur, J., Ott, I., Salassa, L., Ferrari, S., Gasser, G.: DNA intercalating RuII polypyridyl complexes as effective photosensitizers in photodynamic therapy. Chem. Eur. J. 20(44), 14421–14436 (2014)
Pierroz, V., Rubbiani, R., Gentili, C., Patra, M., Mari, C., Gasser, G., Ferrari, S.: Dual mode of cell death upon the photo-irradiation of a RuII polypyridyl complex in interphase or mitosis. Chem. Sci. 7(9), 6115–6124 (2016)
Fong, J., Kasimova, K., Arenas, Y., Kaspler, P., Lazic, S., Mandel, A., Lilge, L.: A novel class of ruthenium-based photosensitizers effectively kills in vitro cancer cells and in vivo tumors. Photochem. Photobiol. Sci. 14(11), 2014–2023 (2015)
Shi, G., Monro, S., Hennigar, R., Colpitts, J., Fong, J., Kasimova, K., Yin, H., DeCoste, R., Spencer, C., Chamberlain, L., Mandel, A., Lilge, L., McFarland, S.A.: Ru(II) dyads derived from α-oligothiophenes: a new class of potent and versatile photosensitizers for PDT. Coord. Chem. Rev. 282-283, 127–138 (2015)
Roundhill, D.M.: Photochemistry, photophysics, and photoredox reactions of Ru(bpy)32+ and related complexes. Photochem. Photophys. Metal Complex., 165–215 (1994)
Kalyanasundaram, K.: Photophysics, photochemistry and solar energy conversion with tris(bipyridyl)ruthenium(II) and its analogues. Coord. Chem. Rev. 46, 159–244 (1982)
Juris, A., Balzani, V., Barigelletti, F., Campagna, S., Belser, P., Von Zelewsky, A.: Ru (II) polypyridine complexes: photophysics, photochemistry, electrochemistry, and chemiluminescence. Coord. Chem. Rev. 84, 85–277 (1988)
Ito, H., Matsui, H.: Mitochondrial reactive oxygen species and photodynamic therapy. Laser Therapy. 25(3), 193–199 (2016)
O’Connor, A.E., Gallagher, W.M., Byrne, A.T.: Porphyrin and nonporphyrin photosensitizers in oncology: preclinical and clinical advances in photodynamic therapy. Photochem. Photobiol. 85(5), 1053–1074 (2009)
De Rosa, F.S., Bentley, M.V.: Photodynamic therapy of skin cancers: sensitizers, clinical studies and future directives. Pharmacol. Res. 17(12), 1447–1455 (2000)
Triesscheijn, M., Baas, P., Schellens, J.H.M., Stewart, F.A.: Photodynamic therapy in oncology. Oncologist. 11(9), 1034–1044 (2006)
Davids, L.M., Kleemann, B.: Combating melanoma: the use of photodynamic therapy as a novel, adjuvant therapeutic tool. Cancer Treat. Rev. 37(6), 465–475 (2011)
Blackmore, L., Moriarty, R., Dolan, C., Adamson, K., Forster, R.J., Devocelle, M., Keyes, T.E.: Peptide directed transmembrane transport and nuclear localization of Ru(II) polypyridyl complexes in mammalian cells. Chem. Commun. 49(26), 2658–2660 (2013)
Barrett, A.J., Kennedy, J.C., Jones, R.A., Nadeau, P., Pottier, R.H.: The effect of tissue and cellular pH on the selective biodistribution of porphyrin-type photochemotherapeutic agents: a volumetric titration study. J. Photochem. Photobiobiol. B. 6(3), 309–323 (1990)
Azzouzi, A.-R., Vincendeau, S., Barret, E., Cicco, A., Kleinclauss, F., van der Poel, H.G., Stief, C.G., Rassweiler, J., Salomon, G., Solsona, E., Alcaraz, A., Tammela, T.T., Rosario, D.J., Gomez-Veiga, F., Ahlgren, G., Benzaghou, F., Gaillac, B., Amzal, B., Debruyne, F.M.J., Fromont, G., Gratzke, C., Emberton, M., PCM301 Study Group: Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial. Lancet Oncol. 18(2), 181–191 (2017)
Vakrat-Haglili, Y., Weiner, L., Brumfeld, V., Brandis, A., Salomon, Y., Mcllroy, B., Wilson, B.C., Pawlak, A., Rozanowska, M., Sarna, T., Scherz, A.: The microenvironment effect on the generation of reactive oxygen species by Pd−bacteriopheophorbide. J. Am. Chem. Soc. 127(17), 6487–6497 (2005)
Jensen, T.J., Vicente, M.G.H., Luguya, R., Norton, J., Fronczek, F.R., Smith, K.M.: Effect of overall charge and charge distribution on cellular uptake, distribution and phototoxicity of cationic porphyrins in HEp2 cells. J. Photochem. Photobiol. B-Biol. 100(2), 100–111 (2010)
Pavani, C., Iamamoto, Y., Baptista, M.S.: Mechanism and efficiency of cell death of type II photosensitizers: effect of zinc chelation. Photochem. Photobiol. 88(4), 774–781 (2012)
Müller-Schiffmann, A., Sticht, H., Korth, C.: Hybrid compounds: from simple combinations to nanomachines. BioDrugs. 26(1), 21–31 (2012)
Ravanat, J.L., Cadet, J., Araki, K., Toma, H.E., Medeiros, M.H.G., Di Mascio, P.: Supramolecular cationic tetraruthenated porphyrin and light-induced decomposition of 2-deoxyguanosine predominantly via a singlet oxygen-mediated mechanism. Photochem. Photobiol. 68(5), 698–702 (1998)
Zhang, J.-X., Zhou, J.-W., Chan, C.-F., Lau, T.C.-K., Kwong, D.W.J., Tam, H.-L., Mak, N.-K., Wong, K.-L., Wong, W.-K.: Comparative studies of the cellular uptake, subcellular localization, and cytotoxic and phototoxic antitumor properties of ruthenium(II)–porphyrin conjugates with different linkers. Bioconjug. Chem. 23(8), 1623–1638 (2012)
Zhu, X., Zhou, H., Liu, Y., Wen, Y., Wei, C., Yu, Q., Liu, J.: Transferrin/aptamer conjugated mesoporous ruthenium nanosystem for redox-controlled and targeted chemo-photodynamic therapy of glioma. Acta Biomater. 82, 143–157 (2018)
Tsubone, T.M., Martins, W.K., Pavani, C., Junqueira, H.C., Itri, R., Baptista, M.S.: Enhanced efficiency of cell death by lysosome-specific photodamage. Sci. Rep. 7(1), 6734 (2017)
Martins, W.K., Santos, N.F., Rocha, C.D.S., Bacellar, I.O.L., Tsubone, T.M., Viotto, A.C., Matsukuma, A.Y., Abrantes, A.B..D.P., Siani, P., Dias, L.G., Baptista, M.S.: Parallel damage in mitochondria and lysosomes is an efficient way to photoinduce cell death. Autophagy. 15(2), 1–21 (2018)
Oliveira, C.S., Turchiello, R., Kowaltowski, A.J., Indig, G.L., Baptista, M.S.: Major determinants of photoinduced cell death: subcellular localization versus photosensitization efficiency. Free Radic. Biol. Med. 51, 824–833 (2011)
Clarke, M., Zhu, F., Frasca, D.: Non-platinum chemotherapeutic metallopharmaceuticals. Chem. Rev. 99(9), 2511–2534 (1999)
Ang, W.H., Dyson, P.J.: Classical and non-classical ruthenium-based anticancer drugs: towards targeted chemotherapy. Eur. J. Inorg. Chem. 2006(20), 4003–4018 (2006)
Schmitt, F., Govindaswamy, P., Suess-Fink, G., Ang, W.H., Dyson, P.J., Juillerat-Jeanneret, L., Therrien, B.: Ruthenium porphyrin compounds for photodynamic therapy of cancer. J. Med. Chem. 51(6), 1811–1816 (2008)
Liu, Y., Ma, K., Jiao, T., Xing, R., Shen, G., Yan, X.: Water-insoluble photosensitizer nanocolloids stabilized by supramolecular interfacial assembly towards photodynamic therapy. Sci. Rep. 7(1), 42978 (2017)
Schmitt, F., Govindaswamy, P., Zava, O., Süss-Fink, G., Juillerat-Jeanneret, L., Therrien, B.: Combined arene ruthenium porphyrins as chemotherapeutics and photosensitizers for cancer therapy. J. Biol. Inorg. Chem. 14(1), 101–109 (2008)
Pernot, M., Bastogne, T., Barry, N.P.E., Therrien, B., Koellensperger, G., Hann, S., Reshetov, V., Barberi-Heyob, M.: Systems biology approach for in vivo photodynamic therapy optimization of ruthenium-porphyrin compounds. J. Photoch. Photobio. B. 117, 80–89 (2012)
Gianferrara, T., Bratsos, I., Iengo, E., Milani, B., Oštrić, A., Spagnul, C., Zangrando, E., Alessio, E.: Synthetic strategies towards ruthenium–porphyrin conjugates for anticancer activity. Dalton Trans. 48, 10742–10756 (2009)
Gianferrara, T., Bergamo, A., Bratsos, I., Milani, B., Spagnul, C., Sava, G., Alessio, E.: Ruthenium−porphyrin conjugates with cytotoxic and phototoxic antitumor activity. J. Med. Chem. 53(12), 4678–4690 (2010)
dos Santos, E.R., Pina, J., Venâncio, T., Serpa, C., Martinho, J.M.G., Carlos, R.M.: Photoinduced energy and electron-transfer reactions by polypyridine ruthenium(II) complexes containing a derivatized perylene diimide. J. Phys. Chem. C. 120(40), 22831–22843 (2016)
de Campos, I.A.S., dos Santos, E.R., Sellani, T.A., Herbozo, C.C.A., Rodrigues, E.G., Roveda Jr., A.C., Pazin, W.M., Ito, A.S., Santana, V.T., Nascimento, O.R., Carlos, R.M.: Influence of the medium on the photochemical and photophysical properties of [Ru(phen) 2(pPDIp)] 2+. ChemPhotoChem. 2(8), 757–764 (2018)
Bacellar, I., Tsubone, T., Pavani, C., Baptista, M.: Photodynamic efficiency: from molecular photochemistry to cell death. Int. J. Mol. Sci. 16(9), 20523–20559 (2015)
Redmond, R.W., Kochevar, I.E.: Spatially resolved cellular responses to singlet oxygen. Photochem. Photobiol. 82(5), 1178–1186 (2006)
Chen, T., Liu, Y., Zheng, W.-J., Liu, J., Wong, Y.-S.: Ruthenium polypyridyl complexes that induce mitochondria-mediated apoptosis in cancer cells. Inorg. Chem. 49(14), 6366–6368 (2010)
Xu, L., Zhang, P.-P., Fang, X.-Q., Liu, Y., Wang, J.-Q., Zhou, H.-Z., Chen, S.-T., Chao, H.: A ruthenium(II) complex containing a p-cresol group induces apoptosis in human cervical carcinoma cells through endoplasmic reticulum stress and reactive oxygen species production. J. Inorg. Biochem. 191, 126–134 (2018)
Zava, O., Zakeeruddin, S.M., Danelon, C., Vogel, H., Grätzel, M., Dyson, P.J.: A cytotoxic ruthenium tris(bipyridyl) complex that accumulates at plasma membranes. Chembiochem. 10(11), 1796–1800 (2009)
Dickerson, M., Sun, Y., Howerton, B., Glazer, E.C.: Modifying charge and hydrophilicity of simple Ru(II) polypyridyl complexes radically alters biological activities: old complexes, surprising new tricks. Inorg. Chem. 53(19), 10370–10377 (2014)
Lv, W., Zhang, Z., Zhang, K.Y., Yang, H., Liu, S., Xu, A., Guo, S., Zhao, Q., Huang, W.: A mitochondria-targeted photosensitizer showing improved photodynamic therapy effects under hypoxia. Angew. Chem. Int. Ed. 55(34), 9947–9951 (2016)
Kalinina, S., Breymayer, J., Reeß, K., Lilge, L., Mandel, A., Rück, A.: Correlation of intracellular oxygen and cell metabolism by simultaneous PLIM of phosphorescent TLD1433 and FLIM of NAD(P)H. J. Biophotonics. 11(10), e201800085–e201800035 (2018)
Huang, H., Yu, B., Zhang, P., Huang, J., Chen, Y., Gasser, G., Ji, L., Chao, H.: Highly charged ruthenium(II) polypyridyl complexes as lysosome-localized photosensitizers for two-photon photodynamic therapy. Angew. Chem. Int. Ed. 54(47), 14049–14052 (2015)
Liu, J., Chen, Y., Li, G., Zhang, P., Jin, C., Zeng, L., Ji, L., Chao, H.: Ruthenium(II) polypyridyl complexes as mitochondria-targeted two-photon photodynamic anticancer agents. Biomaterials. 56(C), 140–153 (2015)
Chakrabortty, S., Agrawalla, B.K., Stumper, A., Vegi, N.M., Fischer, S., Reichardt, C., Kögler, M., Dietzek, B., Feuring-Buske, M., Buske, C., Rau, S., Weil, T.: Mitochondria targeted protein-ruthenium photosensitizer for efficient photodynamic applications. J. Am. Chem. Soc. 139(6), 2512–2519 (2017)
Dolmans, D.E.J.G.J., Fukumura, D., Jain, R.K.: Photodynamic therapy for cancer. Nat. Rev. Cancer. 3, 380 (2003)
Gilkes, D.M., Semenza, G.L., Wirtz, D.: Hypoxia and the extracellular matrix: drivers of tumour metastasis. Nat. Rev. Cancer. 14, 430 (2014)
Bednarski, P.J., Mackay, F.S., Sadler, P.J.: Photoactivatable platinum complexes. Anti Cancer Agents Med. Chem. 7(1), 75–93 (2007)
Joshi, T., Pierroz, V., Mari, C., Gemperle, L., Ferrari, S., Gasser, G.: A bis(dipyridophenazine)(2-(2-pyridyl)pyrimidine-4-carboxylic acid)ruthenium(II) complex with anticancer action upon photodeprotection. Angew. Chem. Int. Ed. 53(11), 2960–2963 (2014)
White, J.K., Schmehl, R.H., Turro, C.: An overview of photosubstitution reactions of Ru(II) imine complexes and their application in photobiology and photodynamic therapy. Inorg. Chim. Acta. 454, 7–20 (2017)
Goldbach, R.E., Rodriguez-Garcia, I., van Lenthe, J.H., Siegler, M.A., Bonnet, S.: N-Acetylmethionine and biotin as photocleavable protective groups for ruthenium polypyridyl complexes. Chem. 17(36), 9924–9929 (2011)
Zayat, L., Noval, M.G., Campi, J., Calero, C.I., Calvo, D.J., Etchenique, R.: A new inorganic photolabile protecting group for highly efficient visible light GABA uncaging. Chembiochem. 8(17), 2035–2038 (2007)
Howerton, B.S., Heidary, D.K., Glazer, E.C.: Strained ruthenium complexes are potent light-activated anticancer agents. J. Am. Chem. Soc. 134(20), 8324–8327 (2012)
Collin, J.-P., Jouvenot, D., Koizumi, M., Sauvage, J.-P.: Ru(phen)2(bis-thioether)2+ complexes: synthesis and photosubstitution reactions. Inorg. Chim. Acta. 360(3), 923–930 (2007)
Garner, R.N., Gallucci, J.C., Dunbar, K.R., Turro, C.: [Ru(bpy)2(5-cyanouracil)2]2+ as a potential light-activated dual-action therapeutic agent. Inorg. Chem. 50(19), 9213–9215 (2011)
Ragazzon, G., Bratsos, I., Alessio, E., Salassa, L., Habtemariam, A., McQuitty, R.J., Clarkson, G.J., Sadler, P.J.: Design of photoactivatable metallodrugs: selective and rapid light-induced ligand dissociation from half-sandwich [Ru([9]aneS3)(N–N′)(py)]2+ complexes. Inorg. Chim. Acta. 393(0), 230–238 (2012)
McClure, B.A., Rack, J.J.: Isomerization in photochromic ruthenium sulfoxide complexes. Eur. J. Inorg. Chem. 2010(25), 3895–3904 (2010)
Zayat, L., Salierno, M., Etchenique, R.: Ruthenium(II) Bipyridyl complexes as photolabile caging groups for amines. Inorg. Chem. 45(4), 1728–1731 (2006)
Sgambellone, M.A., David, A., Garner, R.N., Dunbar, K.R., Turro, C.: Cellular toxicity induced by the photorelease of a caged bioactive molecule: design of a potential dual-action Ru(II) complex. J. Am. Chem. Soc. 135(30), 11274–11282 (2013)
Li, A., Yadav, R., White, J.K., Herroon, M.K., Callahan, B.P., Podgorski, I., Turro, C., Scott, E.E., Kodanko, J.J.: Illuminating cytochrome P450 binding: Ru(ii)-caged inhibitors of CYP17A1. Chem. Commun. 53(26), 3673–3676 (2017)
Hazel, C., Ghrayche, J.B., Wei, J., Renfrew, A.: Photolabile ruthenium(II)–purine complexes: phototoxicity, DNA binding, and light-triggered drug release. Eur. J. Inorg. Chem. 2017(12), 1679–1686 (2017)
Karaoun, N., Renfrew, A.K.: A luminescent ruthenium(ii) complex for light-triggered drug release and live cell imaging. Chem. Commun. 51(74), 14038–14041 (2015)
Albani, B.A., Peña, B., Leed, N.A., de Paula, N.A.B..G., Pavani, C., Baptista, M.S., Dunbar, K.R., Turro, C.: Marked improvement in photoinduced cell death by a new tris-heteroleptic complex with dual action: singlet oxygen sensitization and ligand dissociation. J. Am. Chem. Soc. 136(49), 17095–17101 (2014)
Laemmel, A.-C., Collin, J.-P., Sauvage, J.-P.: Efficient and selective photochemical labilization of a given bidentate ligand in mixed ruthenium(II) complexes of the Ru(phen)2L2+ and Ru(bipy)2L2+ family (L = sterically hindering chelate). Eur. J. Inorg. Chem. 1999(3), 383–386 (1999)
Bonnet, S., Collin, J.P., Sauvage, J.P., Schofield, E.: Photochemical expulsion of the neutral monodentate ligand L in Ru(terpy*)(diimine)(L)(2+): a dramatic effect of the steric properties of the spectator diimine ligand. Inorg. Chem. 43(26), 8346–8354 (2004)
Collin, J.P., Sauvage, J.P.: Synthesis and study of mononuclear ruthenium(II) complexes of sterically hindering diimine chelates. Implications for the catalytic oxidation of water to molecular oxygen. Inorg. Chem. 25(2), 135–141 (1986)
Baranoff, E., Collin, J.-P., Furusho, J., Furusho, Y., Laemmel, A.-C., Sauvage, J.-P.: Photochemical or thermal chelate exchange in the ruthenium coordination sphere of complexes of the Ru(phen)2L family (L = Diimine or Dinitrile ligands). Inorg. Chem. 41(5), 1215–1222 (2002)
Collin, J.-P., Jouvenot, D., Koizumi, M., Sauvage, J.-P.: A ruthenium(II)-complexed rotaxane whose ring incorporates a 6,6′-diphenyl-2,2′-bipyridine: synthesis and light-driven motions. Eur. J. Inorg. Chem. 2005(10), 1850–1855 (2005)
Azar, D., Audi, H., Farhat, S., El Sibai, M., Abi-Habib, R., Khnayzer, R.S.: Phototoxicity of strained Ru(II) complexes: is it the metal complex or the dissociating ligand? Dalton Trans. 46(35), 11529–11532 (2017)
Cuello-Garibo, J.-A., Meijer, M.S., Bonnet, S.: To cage or to be caged? The cytotoxic species in ruthenium-based photoactivated chemotherapy is not always the metal. Chem. Commun. 53(50), 6768–6771 (2017)
Kohler, L., Nease, L., Vo, P., Garofolo, J., Heidary, D.K., Thummel, R.P., Glazer, E.C.: Photochemical and photobiological activity of Ru(II) homoleptic and heteroleptic complexes containing methylated bipyridyl-type ligands. Inorg. Chem. 56(20), 12214–12223 (2017)
van Rixel, V.H.S., Siewert, B., Hopkins, S.L., Askes, S.H.C., Busemann, A., Siegler, M.A., Bonnet, S.: Green light-induced apoptosis in cancer cells by a tetrapyridyl ruthenium prodrug offering two trans coordination sites. Chem. Sci. 7(8), 4922–4929 (2016)
Peña, B., David, A., Pavani, C., Baptista, M.S., Pellois, J.-P., Turro, C., Dunbar, K.R.: Cytotoxicity studies of cyclometallated ruthenium(II) compounds: new applications for ruthenium dyes. Organometallics. 33(5), 1100–1103 (2014)
Palmer, A.M., Pena, B., Sears, R.B., Chen, O., El Ojaimi, M., Thummel, R.P., Dunbar, K.R., Turro, C.: Cytotoxicity of cyclometallated ruthenium complexes: the role of ligand exchange on the activity. Philos. Trans. R. Soc. A Math. Phys. Eng. Sci. 371(1995), 20120135–20120135 (2013)
Wachter, E., Heidary, D.K., Howerton, B.S., Parkin, S., Glazer, E.C.: Light-activated ruthenium complexes photobind DNA and are cytotoxic in the photodynamic therapy window. Chem. Commun. 48(77), 9649–9651 (2012)
Cuello-Garibo, J.-A., James, C.C., Siegler, M.A., Bonnet, S.: Ruthenium-based PACT compounds based on an N,S non-toxic ligand: a delicate balance between photoactivation and thermal stability. Chem. Squar. 1, 2–19 (2017)
Lameijer, L.N., Ernst, D., Hopkins, S.L., Meijer, M.S., Askes, S.H.C., Le Dévédec, S.E., Bonnet, S.: A red light-activated ruthenium-caged NAMPT inhibitor remains phototoxic in hypoxic cancer cells. Angew. Chem. Int. Ed. 56(38), 11549–11553 (2017)
Sainuddin, T., McCain, J., Pinto, M., Yin, H., Gibson, J., Hetu, M., McFarland, S.A.: Organometallic Ru(II) photosensitizers derived from π-expansive cyclometalating ligands: surprising theranostic PDT effects. Inorg. Chem. 55(1), 83–95 (2016)
Yin, H., Stephenson, M., Gibson, J., Sampson, E., Shi, G., Sainuddin, T., Monro, S., McFarland, S.A.: In vitro multiwavelength PDT with 3IL states: teaching old molecules new tricks. Inorg. Chem. 53(9), 4548–4559 (2014)
Hess, J., Huang, H., Kaiser, A., Pierroz, V., Blacque, O., Chao, H., Gasser, G.: Evaluation of the medicinal potential of two ruthenium(II) polypyridine complexes as one- and two-photon photodynamic therapy photosensitizers. Chem. Eur. J. 23(41), 9888–9896 (2017)
Lameijer, L.N., Hopkins, S.L., Brevé, T.G., Askes, S.H.C., Bonnet, S.: d- versus l-glucose conjugation: mitochondrial targeting of a light-activated dual-mode-of-action ruthenium-based anticancer prodrug. Chem. Eur. J. 22, 18484–18491 (2016)
Sainuddin, T., Pinto, M., Yin, H., Hetu, M., Colpitts, J., McFarland, S.A.: Strained ruthenium metal–organic dyads as photocisplatin agents with dual action. J. Inorg. Biochem. 158(C), 45–54 (2016)
Loftus, L.M., White, J.K., Albani, B.A., Kohler, L., Kodanko, J.J., Thummel, R.P., Dunbar, K.R., Turro, C.: New Ru II complex for dual activity: photoinduced ligand release and 1O 2 production. Chem. Eur. J. 22(11), 3704–3708 (2016)
Arenas, Y., Monro, S., Shi, G., Mandel, A., McFarland, S., Lilge, L.: Photodynamic inactivation of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus with Ru(II)-based type I/type II photosensitizers. Photodiagn. Photodyn. Ther. 10(4), 615–625 (2013)
Broekgaarden, M., Weijer, R., van Gulik, T.M., Hamblin, M.R., Heger, M.: Tumor cell survival pathways activated by photodynamic therapy: a molecular basis for pharmacological inhibition strategies. Cancer Metastasis Rev. 34(4), 643–690 (2015)
Sullivan, R., Pare, G.C., Frederiksen, L.J., Semenza, G.L., Graham, C.H.: Hypoxia-induced resistance to anticancer drugs is associated with decreased senescence and requires hypoxia-inducible factor-1 activity. Mol. Cancer Ther. 7(7), 1961–1973 (2008)
Theodoropoulos, V.E., Lazaris, A.C., Kastriotis, I., Spiliadi, C., Theodoropoulos, G.E., Tsoukala, V., Patsouris, E., Sofras, F.: Evaluation of hypoxia-inducible factor 1alpha overexpression as a predictor of tumour recurrence and progression in superficial urothelial bladder carcinoma. BJU Int. 95(3), 425–431 (2005)
Hopkins, S.L., Siewert, B., Askes, S.H.C., Veldhuizen, P., Zwier, R., Heger, M., Bonnet, S.: An in vitro cell irradiation protocol for testing photopharmaceuticals and the effect of blue, green, and red light on human cancer cell lines. Photochem. Photobiol. Sci. 15(5), 644–653 (2016)
Bashkatov, A.N., Genina, E.A., Kochubey, V.I., Tuchin, V.V.: Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm. J. Phys. D. Appl. Phys. 38(15), 2543–2555 (2005)
Hemmer, E., Benayas, A., Légaré, F., Vetrone, F.: Exploiting the biological windows: current perspectives on fluorescent bioprobes emitting above 1000 nm. Nanoscale Horizons. 1(3), 168–184 (2016)
Vogel, A., Venugopalan, V.: Mechanisms of pulsed laser ablation of biological tissues. Chem. Rev. 103(2), 577–644 (2003)
Woods, J.J., Cao, J., Lippert, A.R., Wilson, J.J.: Characterization and biological activity of a hydrogen sulfide-releasing red light-activated ruthenium(II) complex. J. Am. Chem. Soc. 140(39), 12383–12387 (2018)
Sun, W., Wen, Y., Thiramanas, R., Chen, M., Han, J., Gong, N., Wagner, M., Jiang, S., Meijer, M.S., Bonnet, S., Butt, H.-J., Mailänder, V., Liang, X.-J., Wu, S.: Red-light-controlled release of drug–Ru complex conjugates from metallopolymer micelles for phototherapy in hypoxic tumor environments. Adv. Funct. Mater. 28(39), 1804227 (2018)
Sun, W., Thiramanas, R., Slep, L.D., Zeng, X., Mailänder, V., Wu, S.: Photoactivation of anticancer Ru complexes in deep tissue: how deep can we go? Chem. Eur. J. 23(45), 10832–10837 (2017)
Al-Afyouni, M.H., Rohrabaugh, T.N., Al-Afyouni, K.F., Turro, C.: New Ru(ii) photocages operative with near-IR light: new platform for drug delivery in the PDT window. Chem. Sci. 9(32), 6711–6720 (2018)
Loftus, L.M., Al-Afyouni, K.F., Turro, C.: New RuII scaffold for photoinduced ligand release with red light in the photodynamic therapy (PDT) window. Chem. Eur. J. 24(45), 11550–11553 (2018)
Pawlicki, M., Collins, H.A., Denning, R.G., Anderson, H.L.: Two-photon absorption and the design of two-photon dyes. Angew. Chem. Int. Ed. 48(18), 3244–3266 (2009)
Girardot, C., Cao, B., Mulatier, J.-C., Baldeck, P.L., Chauvin, J., Riehl, D., Delaire, J.A., Andraud, C., Lemercier, G.: Ruthenium(II) complexes for two-photon absorption-based optical power limiting. ChemPhysChem. 9(11), 1531–1535 (2008)
Zhou, Z., Liu, J., Rees, T.W., Wang, H., Li, X., Chao, H., Stang, P.J.: Heterometallic Ru–Pt metallacycle for two-photon photodynamic therapy. Proc. Natl. Acad. Sci. USA. 115(22), 5664–5669 (2018)
Askes, S.H.C., Bahreman, A., Bonnet, S.: Activation of a photodissociative ruthenium complex by triplet–triplet annihilation upconversion in liposomes. Angew. Chem. Int. Ed. 53(4), 1029–1033 (2014)
Askes, S.H.C., Meijer, M.S., Bouwens, T., Landman, I., Bonnet, S.: Red light activation of Ru(II) polypyridyl prodrugs via triplet-triplet annihilation upconversion: feasibility in air and through meat. Molecules. 21(11), 1460 (2016)
Kim, J.-H., Kim, J.-H.: Encapsulated triplet–triplet annihilation-based upconversion in the aqueous phase for sub-band-gap semiconductor photocatalysis. J. Am. Chem. Soc. 134(42), 17478–17481 (2012)
Boyer, J.C., van Veggel, F.C.J.M.: Absolute quantum yield measurements of colloidal NaYF4: Er3+, Yb3+ upconverting nanoparticles. Nanoscale. 2(8), 1417–1419 (2010)
Askes, S.H.C., Pomp, W., Hopkins, S.L., Kros, A., Wu, S., Schmidt, T., Bonnet, S.: Imaging upconverting polymersomes in cancer cells: biocompatible antioxidants brighten triplet–triplet annihilation upconversion. Small. 12(40), 5579–5590 (2016)
Askes, S.H.C., Bonnet, S.: Solving the oxygen sensitivity of sensitized photon upconversion in life science applications. Nat. Rev. Chem. 2, 437–452 (2018)
Ruggiero, E., Garino, C., Mareque-Rivas, J.C., Habtemariam, A., Salassa, L.: Upconverting nanoparticles prompt remote near-infrared photoactivation of Ru(II)-arene complexes. Chem. Eur. J. 22(8), 2801–2811 (2016)
Ruggiero, E., Habtemariam, A., Yate, L., Mareque Rivas, J., Salassa, L.: Near infrared photolysis of a Ru polypyridyl complex by upconverting nanoparticles. Chem. Commun. 50(14), 1715–1718 (2014)
Ruggiero, E., Hernández-Gil, J., Mareque-Rivas, J.C., Salassa, L.: Near infrared activation of an anticancer Pt(IV) complex by Tm-doped upconversion nanoparticles. Chem. Commun. 51(11), 2091–2094 (2015)
Perfahl, S., Natile, M.M., Mohamad, H.S., Helm, C.A., Schulzke, C., Natile, G., Bednarski, P.J.: Photoactivation of diiodido-Pt(IV) complexes coupled to upconverting nanoparticles. Mol. Pharm. 13(7), 2346–2362 (2016)
Bown, S.G., Rogowska, A.Z., Whitelaw, D.E., Lees, W.R., Lovat, L.B., Ripley, P., Jones, L., Wyld, P., Gillams, A., Hatfield, A.W.R.: Photodynamic therapy for cancer of the pancreas. Gut. 50(4), 549–557 (2002)
Karakullukcu, B., van Veen, R.L.P., Aans, J.B., Hamming-Vrieze, O., Navran, A., Teertstra, H.J., van den Boom, F., Niatsetski, Y., Sterenborg, H.J.C.M., Tan, I.B.: MR and CT based treatment planning for mTHPC mediated interstitial photodynamic therapy of head and neck cancer: description of the method. Lasers Surg. Med. 45, 517–523 (2013)
Dupont, C., Mordon, S., Deleporte, P., Reyns, N., Vermandel, M.: A novel device for intraoperative photodynamic therapy dedicated to glioblastoma treatment. Futur. Oncol. 13(27), 2441–2454 (2017)
PhD, S.M., Cochrane, C., Tylcz, J.B., Betrouni, N., Mortier, L., Koncar, V.: Light emitting fabric technologies for photodynamic therapy. Photodiagn. Photodyn. Ther. 12(1), 1–8 (2015)
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Meijer, M.S., Carlos, R.M., Baptista, M.S., Bonnet, S. (2022). Photomedicine with Inorganic Complexes: A Bright Future. In: Bahnemann, D., Patrocinio, A.O.T. (eds) Springer Handbook of Inorganic Photochemistry. Springer Handbooks. Springer, Cham. https://doi.org/10.1007/978-3-030-63713-2_34
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