This review article covers the synthetic strategies, structural aspects, and host-guest properties of ruthenium metalla-assemblies, with a special focus on their use as drug delivery vectors. The two-dimensional metalla-rectangles show interesting host-guest possibilities but seem less appropriate for being used as drug carriers. On the other hand, metalla-prisms allow encapsulation and possible targeted release of bioactive molecules and consequently show some potential as drug delivery vectors. The reactivity of these metalla-prisms can be fine-tuned to allow a fine control of the guest’s release. The larger metalla-cubes can be used to stabilize the formation of G-quadruplex DNA and can be used to encapsulate and release photoactive molecules such as porphins. These metalla-assemblies demonstrate great prospective in photodynamic therapy. 1. Introduction Anticancer platinum complexes dominate the field of metals in cancer chemotherapy, mainly because of the considerable research effort that followed the fortuitous discovery of the anticancer property of cisplatin (Figure 1) in the late 1960s [1]. Unfortunately, the use of cisplatin is restricted because of severe dose-limiting side effects, which arise from the indiscriminate uptake of the drug into all rapidly dividing cells. Indeed the platinum atom is known to efficiently bind to serum proteins, especially human serum albumin (HsA) [2]. Once inside cells, aquated cisplatin species will mainly bind at the N7 position of guanine, leading to significant distortions of the DNA helix [3]. These DNA lesions are thought to prevent replication and transcription and ultimately to lead to cellular apoptosis [3]. Figure 1: The three platinum-based anticancer drugs, cisplatin, carboplatin, and oxaliplatin, which have gained worldwide marketing approval for humans [ 4]. The severe side effects of cisplatin have led to a massive investigation into the cytotoxicity and genotoxicity of platinum-based compounds, in order to elucidate their molecular mechanisms and identify key biomolecular targets for rational drug design [6–8]. In the 30 years since cisplatin’s first approval for human use, only two compounds have been approved worldwide (oxaliplatin and carboplatin, Figure 1) and another three gaining marketing approval in individual nations (Nedaplatin, Lobaplatin, and Heptaplatin) [4]. Currently, there are four mononuclear platinum drugs in various stages of clinical trials, with two of these being close to clinical recognition (satraplatin [9] and picoplatin [10]). Two other drugs (ProLindac and Lipoplatin)
References
[1]
B. Rosenberg, L. van Camp, E. B. Grimley, and A. J. Thomson, “The inhibition of growth or cell division in Escherichia coli by different ionic species of platinum(IV) complexes,” The Journal of Biological Chemistry, vol. 242, no. 6, pp. 1347–1352, 1967.
[2]
L. Kelland, “The resurgence of platinum-based cancer chemotherapy,” Nature Reviews Cancer, vol. 7, no. 8, pp. 573–584, 2007.
[3]
E. R. Jamieson and S. J. Lippard, “Structure, recognition, and processing of cisplatin-DNA adducts,” Chemical Reviews, vol. 99, no. 9, pp. 2467–2498, 1999.
[4]
N. J. Wheate, S. Walker, G. E. Craig, and R. Oun, “The status of platinum anticancer drugs in the clinic and in clinical trials,” Dalton Transactions, vol. 39, no. 35, pp. 8113–8127, 2010.
[5]
J. D. Roberts, J. Peroutka, G. Beggiolin, C. Manzotti, L. Piazzoni, and N. Farrell, “Comparison of cytotoxicity and cellular accumulation of polynuclear platinum complexes in L1210 murine leukemia cell lines,” Journal of Inorganic Biochemistry, vol. 77, no. 1-2, pp. 47–50, 1999.
[6]
J. Reedijk, “Improved understanding in platinium antitumour chemistry,” Chemical Communications, no. 7, pp. 801–806, 1996.
[7]
S. M. Cohen and S. J. Lippard, “Cisplatin: from DNA damage to cancer chemotherapy,” Progress in Nucleic Acid Research and Molecular Biology, vol. 67, pp. 93–130, 2001.
[8]
Z. H. Siddik, “Cisplatin: mode of cytotoxic action and molecular basis of resistance,” Oncogene, vol. 22, no. 47, pp. 7265–7279, 2003.
[9]
L. R. Kelland, G. Abel, M. J. McKeage et al., “Preclinical antitumor evaluation of bis-acetato-ammine-dichloro- cyclohexylamine platinum(IV): an orally active platinum drug,” Cancer Research, vol. 53, no. 11, pp. 2581–2586, 1993.
[10]
J. Holford, F. Raynaud, B. Murrer et al., “Chemical, biochemical and pharmacological activity of the novel sterically hindered platinum co-ordination complex, cis-[amminedichloro(2-methylpyridine)] platinum(II) (AMD473),” Anti-Cancer Drug Design, vol. 13, no. 1, pp. 1–18, 1998.
[11]
S. B. Howell, “The design and development of the tumor-targeting nanopolymer dach platinum conjugate AP5346 (ProlindacTM),” in Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy, A. Bonetti, R. Leone, F. Muggia, and S. B. Howell, Eds., Cancer Drug Discovery and Development, pp. 33–39, Humana Press, New York, NY, USA, 2009.
[12]
M. Serova, A. Ghoul, K. Rezai et al., “In vitro anti-proliferative effects of Prolindac, a novel DACH-platinum linked polymer compound, as a single agent and in combination with other anti-cancer drugs,” in Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy: Molecular Mechanism and Clinical Applications, A. Bonetti, R. Leone, F. Muggia, and S. B. Howell, Eds., pp. 41–47, Humana Press, New York, NY, USA, 2009.
[13]
T. Boulikas, “Low toxicity and anticancer activity of a novel liposomal cisplatin (Lipoplatin) in mouse xenografts,” Oncology Reports, vol. 12, pp. 3–12, 2004.
[14]
T. Boulikas, “Molecular mechanisms of cisplatin and its liposomally encapuslated form, LipoplatinTM as a chemotherapy and antiangiogenesis drug,” Cancer Therapy, vol. 5, pp. 351–376, 2007.
[15]
N. Farrell, Metal Ions in Biolgical Systems, Vol 42: Metal Complexes in Tumor Diagnosis and as Anticancer Agents, 2004.
[16]
P. Perego, L. Gatti, C. Caserini et al., “The cellular basis of the efficacy of the trinuclear platinum complex BBR 3464 against cisplatin-resistant cells,” Journal of Inorganic Biochemistry, vol. 77, no. 1-2, pp. 59–64, 1999.
[17]
J. D. Roberts, J. Peroutka, and N. Farrell, “Cellular pharmacology of polynuclear platinum anti-cancer agents,” Journal of Inorganic Biochemistry, vol. 77, no. 1-2, pp. 51–57, 1999.
[18]
D. I. Jodrell, T. R. J. Evans, W. Steward et al., “Phase II studies of BBR3464, a novel tri-nuclear platinum complex, in patients with gastric or gastro-oesophageal adenocarcinoma,” European Journal of Cancer, vol. 40, no. 12, pp. 1872–1877, 2004.
[19]
N. Bertrand and J. C. Leroux, “The journey of a drug-carrier in the body: an anatomo-physiological perspective,” Journal of Controlled Release, vol. 161, no. 2, pp. 152–163, 2012.
[20]
K. Kataoka, A. Harada, and Y. Nagasaki, “Block copolymer micelles for drug delivery: design, characterization and biological significance,” Advanced Drug Delivery Reviews, vol. 47, no. 1, pp. 113–131, 2001.
[21]
H. Maeda, “The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting,” Advances in Enzyme Regulation, vol. 41, pp. 189–207, 2001.
[22]
H. Uchino, Y. Matsumura, T. Negishi et al., “Cisplatin-incorporating polymeric micelles (NC-6004) can reduce nephrotoxicity and neurotoxicity of cisplatin in rats,” British Journal of Cancer, vol. 93, no. 6, pp. 678–687, 2005.
[23]
K. J. Haxton and H. M. Burt, “Polymeric drug delivery of platinum-based anticancer agents,” Journal of Pharmaceutical Sciences, vol. 98, no. 7, pp. 2299–2316, 2009.
[24]
R. Haag and F. Kratz, “Polymer therapeutics: concepts and applications,” Angewandte Chemie&International Edition, vol. 45, no. 8, pp. 1198–1215, 2006.
[25]
D. E. Discher and A. Eisenberg, “Polymer vesicles,” Science, vol. 297, no. 5583, pp. 967–973, 2002.
[26]
P. Govender, B. Therrien, and G. S. Smith, “Bio-metallodendrimers—emerging strategies in metal-based drug design,” European Journal of Inorganic Chemistry, no. 17, pp. 2853–2862, 2012.
[27]
F. Arnesano and G. Natile, “Mechanistic insight into the cellular uptake and processing of cisplatin 30 years after its approval by FDA,” Coordination Chemistry Reviews, vol. 253, no. 15-16, pp. 2070–2081, 2009.
[28]
S. Bhattacharyya, R. A. Kudgus, R. Bhattacharya, and P. Mukherjee, “Inorganic nanoparticles in cancer therapy,” Pharmaceutical Research, vol. 28, no. 2, pp. 237–259, 2011.
[29]
D. K. Chan, D. M. Lieberman, S. Musatov, J. A. Goldfein, S. H. Selesnick, and M. G. Kaplitt, “Protection against cisplatin-induced ototoxicity by adeno-associated virus-mediated delivery of the X-linked inhibitor of apoptosis protein is not dependent on caspase inhibition,” Otology & Neurotology, vol. 28, no. 3, pp. 417–425, 2007.
[30]
K. Ajima, M. Yudasaka, T. Murakami, A. Maigné, K. Shiba, and S. Iijima, “Carbon nanohorns as anticancer drug carriers,” Molecular Pharmaceutics, vol. 2, no. 6, pp. 475–480, 2005.
[31]
R. P. Feazell, N. Nakayama-Ratchford, H. Dai, and S. J. Lippard, “Soluble single-walled carbon nanotubes as longboat delivery systems for platinum(IV) anticancer drug design,” Journal of the American Chemical Society, vol. 129, no. 27, pp. 8438–8439, 2007.
[32]
B. Therrien, “Arene ruthenium cages: boxes full of surprises,” European Journal of Inorganic Chemistry, vol. 2009, no. 17, pp. 2445–2453, 2009.
[33]
M. Fujita, J. Yazaki, and K. Ogura, “Preparation of a macrocyclic polynuclear complex, [(en)Pd(4, -bpy)]4(NO3)8 (en = ethylenediamine, bpy = bipyridine), which recognizes an organic molecule in aqueous media,” Journal of the American Chemical Society, vol. 112, pp. 5645–5646, 1990.
[34]
M. Fujita, D. Oguro, M. Miyazawa, H. Oka, K. Yamaguchi, and K. Ogura, “Self assembly of ten molecules into nanometre-sized organic host frameworks,” Nature, vol. 378, no. 6556, pp. 469–471, 1995.
[35]
Y. M. Jeon, J. Kim, D. Whang, and K. Kim, “Molecular container assembly capable of conrolling binding and release of its guest molecules: Reversible encapsulation of organic molecules in sodium ion complexed cucurbituril,” Journal of the American Chemical Society, vol. 118, no. 40, pp. 9790–9791, 1996.
[36]
F. A. Cotton, C. Lin, and C. A. Murillo, “Supramolecular arrays based on dimetal building units,” Accounts of Chemical Research, vol. 34, no. 10, pp. 759–771, 2001.
[37]
M. Fujita, M. Tominaga, A. Hori, and B. Therrien, “Coordination assemblies from a Pd(II)-cornered square complex,” Accounts of Chemical Research, vol. 38, no. 4, pp. 369–378, 2005.
[38]
C. Y. Su, Y. P. Cai, C. L. Chen, M. D. Smith, W. Kaim, and H. C. zur Loye, “Ligand-directed molecular architectures: Self-assembly of two-dimensional rectangular metallacycles and three-dimensional trigonal or tetragonal prisms,” Journal of the American Chemical Society, vol. 125, no. 28, pp. 8595–8613, 2003.
[39]
R. Chakrabarty, P. S. Mukherjee, and P. J. Stang, “Supramolecular coordination: self-assembly of finite two- and three-dimensional ensembles,” Chemical Reviews, vol. 111, no. 11, pp. 6810–6918, 2011.
[40]
J. E. M. Lewis, E. L. Gavey, S. A. Cameron, and J. D. Crowley, “Stimuli-responsive Pd2L4 metallosupramolecular cages: towards targeted cisplatin drug delivery,” Chemical Science, vol. 3, no. 3, pp. 778–784, 2012.
[41]
F. P. Dwyer, E. C. Gyarfas, W. P. Rogers, and J. H. Koch, “Biological activity of complex ions,” Nature, vol. 170, no. 4318, pp. 190–191, 1952.
[42]
M. J. Clarke, “Oncological implications of the chemistry of ruthenium,” Metals Ions in Biological System, vol. 11, pp. 231–283, 1980.
[43]
E. S. Antonarakis and A. Emadi, “Ruthenium-based chemotherapeutics: are they ready for prime time?” Cancer Chemotherapy and Pharmacology, vol. 66, no. 1, pp. 1–9, 2010.
[44]
A. Bergamo and G. Sava, “Ruthenium anticancer compounds: myths and realities of the emerging metal-based drugs,” Dalton Transactions, vol. 40, no. 31, pp. 7817–7823, 2011.
[45]
W. H. Ang, A. Casini, G. Sava, and P. J. Dyson, “Organometallic ruthenium-based antitumor compounds with novel modes of action,” Journal of Organometallic Chemistry, vol. 696, no. 5, pp. 989–998, 2011.
[46]
J. M. Rademaker-Lakhai, D. van den Bongard, D. Pluim, J. H. Beijnen, and J. H. M. Schellens, “A phase I and pharmacological study with imidazolium-trans-DMSO-imidazole-tetrachlororuthenate, a novel ruthenium anticancer agent,” Clinical Cancer Research, vol. 10, no. 11, pp. 3717–3727, 2004.
[47]
C. G. Hartinger, M. A. Jakupec, S. Zorbas-Seifried et al., “KP1019, a new redox-active anticancer agent—preclinical development and results of a clinical phase I study in tumor patients,” Chemistry and Biodiversity, vol. 5, no. 10, pp. 2140–2155, 2008.
[48]
P. Heffeter, B. Atil, K. Kryeziu et al., “The ruthenium compound KP1339 potentiates the anticancer activity of sorafenib in vitro and in vivo,” European Journal of Cancer, vol. 49, no. 15, pp. 3366–3375, 2013.
[49]
G. Süss-Fink, “Arene ruthenium complexes as anticancer agents,” Dalton Transactions, vol. 39, no. 7, pp. 1673–1688, 2010.
[50]
C. S. Allardyce, P. J. Dyson, D. J. Ellis, and S. L. Heath, “[Ru(eta)6-p-cymene)Cl-2(pta)] (pta=1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane): a water soluble compound that exhibits pH dependent DNA binding providing selectivity for diseased cells,” Chemical Communications, pp. 1396–1397, 2001.
[51]
C. Scolaro, A. Bergamo, L. Brescacin et al., “In vitro and in vivo evaluation of ruthenium(II)-arene PTA complexes,” Journal of Medicinal Chemistry, vol. 48, no. 12, pp. 4161–4171, 2005.
[52]
W. H. Ang, E. Daldini, C. Scolaro, R. Scopelliti, L. Juillerat-Jeannerat, and P. J. Dyson, “Development of organometallic ruthenium-arene anticancer drugs that resist hydrolysis,” Inorganic Chemistry, vol. 45, no. 22, pp. 9006–9013, 2006.
[53]
R. E. Aird, J. Cummings, A. A. Ritchie et al., “In vitro and in vivo activity and cross resistance profiles of novel ruthenium (II) organometallic arene complexes in human ovarian cancer,” British Journal of Cancer, vol. 86, no. 10, pp. 1652–1657, 2002.
[54]
R. A. Zelonka and M. C. Baird, “Reactions of benzene complexes of ruthernium(II),” Journal of Organometallic Chemistry, vol. 35, no. 1, pp. C43–C46, 1972.
[55]
G. Süss-Fink, “Water-soluble arene ruthenium complexes: from serendipity to catalysis and drug design,” Journal of Organometallic Chemistry, vol. 751, pp. 2–19, 2014.
[56]
G. Süss-Fink and B. Therrien, “Dinuclear ruthenium and osmium arene trihydrido complexes: versatile water-soluble synthons in organometallic chemistry,” Organometallics, vol. 26, no. 4, pp. 766–774, 2007.
[57]
F. A. Egbewande, L. E. H. Paul, B. Therrien, and J. Furrer, “Synthesis, characterization and cytotoxicity of ( -p-cymene)ruthenium(II) complexes of -amino acids,” European Journal of Inorganic Chemistry, vol. 2014, no. 7, pp. 1174–1184, 2014.
[58]
H. Yan, G. Süss-Fink, A. Neels, and H. Stoeckli-Evans, “Mono-, di- and tetra-nuclear p-cymeneruthenium complexes containing oxalato ligands,” Journal of the Chemical Society, Dalton Transactions, vol. 1997, no. 22, pp. 4345–4350, 1997.
[59]
F. Linares, M. A. Galindo, S. Galli, M. A. Romero, J. A. R. Navarro, and E. Barea, “Tetranuclear coordination assemblies based on half-sandwich ruthenium(II) complexes: noncovalent binding to DNA and cytotoxicity,” Inorganic Chemistry, vol. 48, no. 15, pp. 7413–7420, 2009.
[60]
J. Mattsson, P. Govindaswamy, A. K. Renfrew et al., “Synthesis, molecular structure and anticancer activity of cationic arene ruthenium metallarectangles,” Organometallics, vol. 28, no. 15, pp. 4350–4357, 2009.
[61]
B. H. Northrop, Y.-R. Zheng, K.-W. Chi, and P. J. Stang, “Self-organization in coordination-driven self-assembly,” Accounts of Chemical Research, vol. 42, no. 10, pp. 1554–1563, 2009.
[62]
V. Vajpayee, Y. H. Song, M. H. Lee et al., “Self-assembled arene-ruthenium-based rectangles for the selective sensing of multi-carboxylate anions,” Chemistry, vol. 17, no. 28, pp. 7837–7844, 2011.
[63]
V. Vajpayee, Y. H. Song, Y. J. Jung et al., “Coordination-driven self-assembly of ruthenium-based molecular-rectangles: synthesis, characterization, photo-physical and anticancer potency studies,” Dalton Transactions, vol. 41, no. 10, pp. 3046–3052, 2012.
[64]
V. Vajpayee, S. Lee, S. Kim et al., “Self-assembled metalla-rectangles bearing azodipyridyl ligands: synthesis, characterization and antitumor activity,” Dalton Transactions, vol. 42, no. 2, pp. 466–475, 2013.
[65]
V. Vajpayee, S. M. Lee, J. W. Park et al., “Growth inhibitory activity of a bis-benzimidazole-bridged arene ruthenium metalla-rectangle and -prism,” Organometallics, vol. 32, no. 6, pp. 1563–1566, 2013.
[66]
N. P. E. Barry, F. Edafe, and B. Therrien, “Anticancer activity of tetracationic arene ruthenium metalla-cycles,” Dalton Transactions, vol. 40, no. 27, pp. 7172–7180, 2011.
[67]
G. Gupta, B. Murray, P. Dyson, and B. Therrien, “Synthesis, molecular structure and cytotoxicity of molecular materials based on water soluble half-sandwich Rh(III) and Ir(III) tetranuclear metalla-cycles,” Materials, vol. 6, no. 11, pp. 5352–5366, 2013.
[68]
N. P. E. Barry, F. Edafe, P. J. Dyson, and B. Therrien, “Anticancer activity of osmium metalla-rectangles,” Dalton Transactions, vol. 39, no. 11, pp. 2816–2820, 2010.
[69]
P. Govindaswamy, D. Linder, J. Lacour, G. Süss-Fink, and B. Therrien, “Self-assembled hexanuclear arene ruthenium metallo-prisms with unexpected double helical chirality,” Chemical Communications, no. 45, pp. 4691–4693, 2006.
[70]
N. P. E. Barry, M. Austeri, J. Lacour, and B. Therrien, “Highly efficient NMR enantiodiscrimination of chiral octanuclear metalla-boxes in polar solvent,” Organometallics, vol. 28, no. 16, pp. 4894–4897, 2009.
[71]
N. P. E. Barry, N. H. Abd Karim, R. Vilar, and B. Therrien, “Interactions of ruthenium coordination cubes with DNA,” Dalton Transactions, no. 48, pp. 10717–10719, 2009.
[72]
N. P. E. Barry, J. Furrer, J. Freudenreich, G. Süss-Fink, and B. Therrien, “Designing the host-guest properties of tetranuclear arene ruthenium metalla-rectangles to accommodate a pyrene molecule,” European Journal of Inorganic Chemistry, vol. 2010, no. 5, pp. 725–728, 2010.
[73]
C. S. Johnson, “Diffusion ordered nuclear magnetic resonance spectroscopy: principles and applications,” Progress in Nuclear Magnetic Resonance Spectroscopy, vol. 34, no. 3-4, pp. 203–256, 1999.
[74]
Y. Cohen, L. Avram, and L. Frish, “Diffusion NMR spectroscopy in supramolecular and combinatorial chemistry: an old parameter—new insights,” Angewandte Chemie, vol. 44, no. 4, pp. 520–554, 2005.
[75]
N. P. E. Barry, J. Furrer, and B. Therrien, “In- and out-of-cavity interactions by modulating the size of ruthenium metallarectangles,” Helvetica Chimica Acta, vol. 93, no. 7, pp. 1313–1328, 2010.
[76]
P. Govindaswamy, J. Furrer, G. Süss-Fink, and B. Therrien, “Encapsulation of triphenylene derivatives in the hexanuclear arene ruthenium metallo-prismatic cage [Ru6(p-PriC6H4Me)6(tpt)2(dhbq)3]6+ (tpt？=？2,4,6-tri(pyridin-4-yl)-1,3,5-triazine, dhbq？=？2,5-dihydroxy-1,4-benzoquinonato),” Zeitschrift für Anorganische und Allgemeine Chemie, vol. 634, no. 8, pp. 1349–1352, 2008.
[77]
J. Mattsson, P. Govindaswamy, J. Furrer et al., “Encapsulation of aromatic molecules in hexanuclear arene ruthenium cages: a strategy to build up organometallic carceplex prisms with a dangling arm standing out,” Organometallics, vol. 27, no. 17, pp. 4346–4356, 2008.
[78]
N. P. E. Barry and B. Therrien, “Host-guest chemistry in the hexanuclear (arene)ruthenium metalla-prismatic cage [Ru6(p-cymene)6(tpt)2(dhnq)3]6+,” European Journal of Inorganic Chemistry, vol. 2009, no. 31, pp. 4695–4700, 2009.
[79]
J. Freudenreich, N. P. E. Barry, G. Süss-Fink, and B. Therrien, “Permanent encapsulation or host-guest behavior of aromatic molecules in hexanuclear arene ruthenium prisms,” European Journal of Inorganic Chemistry, vol. 2010, no. 16, pp. 2400–2405, 2010.
[80]
B. Therrien, G. Süss-Fink, P. Govindaswamy, A. K. Renfrew, and P. J. Dyson, “The “complex-in-a-complex” cations [(acac)2M？Ru6(p-iPrC6H4Me)6(tpt)2(dhbq)3]6+: a trojan horse for cancer cells,” Angewandte Chemie—International Edition, vol. 47, no. 20, pp. 3773–3776, 2008.
[81]
J. Mattsson, O. Zava, A. K. Renfrew et al., “Drug delivery of lipophilic pyrenyl derivatives by encapsulation in a water soluble metalla-cage,” Dalton Transactions, vol. 39, no. 35, pp. 8248–8255, 2010.
[82]
N. P. E. Barry, O. Zava, P. J. Dyson, and B. Therrien, “Excellent correlation between drug release and portal size in metalla-cage drug-delivery systems,” Chemistry, vol. 17, no. 35, pp. 9669–9677, 2011.
[83]
K. D. Tew, “Glutathione-associated enzymes in anticancer drug resistance,” Cancer Research, vol. 54, no. 16, pp. 4313–4320, 1994.
[84]
D. M. Townsend and K. D. Tew, “The role of glutathione-S-transferase in anti-cancer drug resistance,” Oncogene, vol. 22, no. 47, pp. 7369–7375, 2003.
[85]
A. Pitto-Barry, N. P. E. Barry, O. Zava, R. Deschenaux, and B. Therrien, “Encapsulation of pyrene-functionalized poly(benzyl ether) dendrons into a water-soluble organometallic cage,” Chemistry: An Asian Journal, vol. 6, no. 6, pp. 1595–1603, 2011.
[86]
A. Pitto-Barry, N. P. E. Barry, O. Zava, R. Deschenaux, P. J. Dyson, and B. Therrien, “Double targeting of tumours with pyrenyl-modified dendrimers encapsulated in an arene-ruthenium metallaprism,” Chemistry—A European Journal, vol. 17, no. 6, pp. 1966–1971, 2011.
[87]
A. Pitto-Barry, O. Zava, P. J. Dyson, R. Deschenaux, and B. Therrien, “Enhancement of cytotoxicity by combining pyrenyl-dendrimers and arene ruthenium metallacages,” Inorganic Chemistry, vol. 51, no. 13, pp. 7119–7124, 2012.
[88]
B. W. Henderson and T. J. Dougherty, “How does photodynamic therapy work?” Photochemistry and Photobiology, vol. 55, no. 1, pp. 145–157, 1992.
[89]
T. J. Dougherty, C. J. Gomer, B. W. Henderson et al., “Photodynamic therapy,” Journal of the National Cancer Institute, vol. 90, no. 12, pp. 889–905, 1998.
[90]
M. Ferrari, “Cancer nanotechnology: opportunities and challenges,” Nature Reviews Cancer, vol. 5, no. 3, pp. 161–171, 2005.
[91]
J. Freudenreich, C. Dalvit, G. Süss-Fink, and B. Therrien, “Encapsulation of photosensitizers in hexa- and octanuclear organometallic cages: synthesis and characterization of carceplex and host-guest systems in solution,” Organometallics, vol. 32, no. 10, pp. 3018–3033, 2013.
[92]
B. Therrien, “Transporting and shielding photosensitisers by using water-soluble organometallic cages: a new strategy in drug delivery and photodynamic therapy,” Chemistry, vol. 19, no. 26, pp. 8378–8386, 2013.
[93]
F. Schmitt, J. Freudenreich, N. P. E. Barry, L. Juillerat-Jeanneret, G. Süss-Fink, and B. Therrien, “Organometallic cages as vehicles for intracellular release of photosensitizers,” Journal of the American Chemical Society, vol. 134, no. 2, pp. 754–757, 2012.
[94]
L. E. H. Paul, B. Therrien, and J. Furrer, “Investigation of the reactivity between a ruthenium hexacationic prism and biological ligands,” Inorganic Chemistry, vol. 51, no. 2, pp. 1057–1067, 2012.
[95]
L. E. H. Paul, B. Therrien, J. Furrer, and J. Biol, “Interaction of a ruthenium hexacationic prism with amino acids and biological ligands: ESI mass spectrometry and NMR characterisation of the reaction products,” Journal of Biological Inorganic Chemistry, vol. 17, no. 7, pp. 1053–1062, 2012.
[96]
M. Hanif, H. Henke, S. M. Meier et al., “Is the reactivity of M(II)-arene complexes of 3-hydroxy-2(1 H)-pyridones to biomolecules the anticancer activity determining paramete？,” Inorganic Chemistry, vol. 49, no. 17, pp. 7953–7963, 2010.
[97]
L. E. H. Paul, J. Furrer, and B. Therrien, “Reactions of a cytotoxic hexanuclear arene ruthenium assembly with biological ligands,” Journal of Organometallic Chemistry, vol. 734, pp. 45–52, 2013.
