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Progress in the Utilisation of Organometallic Compounds in the Development of Cancer Drugs


Authors: H. Skoupilová;  R. Hrstka
Authors‘ workplace: Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
Published in: Klin Onkol 2019; 32(Supplementum 3): 25-33
Category: Review
doi: https://doi.org/10.14735/amko20193S

Overview

Background: Organometallic compounds are chemical substances containing a carbon-metal bond. From a biological point of view, these compounds are generally considered to be toxic for living organisms. They may exert therapeutic potential, especially as anticancer or antimicrobial drugs. Their structural variability and usually uncharged and mostly lipophilic character are particularly advantageous properties. Platinum derivatives (predominately cisplatin) are the most proven advantageous agents in the medical field. The success of cisplatin has led the scientific community to focus on the synthesis of other organometallic compounds with improved anti-tumour effects and lower cytotoxicity towards healthy tissues. Close attention is focused on compounds bearing atoms of iron, titanium or ruthenium.

Purpose: Here, we focus on summarising a description of the most important compounds containing iron, titanium or ruthenium atoms in their structure, showing potential application in cancer treatment including the mechanism of action for some of the most commonly studied compounds. The reported structures were used successfully in preclinical studies including animal models and progressed to various stages of human clinical trials. Despite the fail­ure of some of these compounds, there are still several candidates which are expected to progress to the late stages of the clinical trials either alone or as part of combined chemotherapy. Ruthenium-containing substances in particular show high potential for utilisation in cancer treatment due to low cytotoxicity associated with the ability to block neoangiogenesis and metastasis development.

Keywords:

cancer – chemother­apy – Drugs – organometallic compounds – Titanium – ruthenium


Sources

1. Glusker JP. Dorothy Crowfoot Hodgkin (1910– 1994). Protein Sci 1994; 3(12): 2465– 2469. doi: 10.1002/ pro. 5560031233.

2. Leung HW, Hallesy DW, Shott LD et al. Toxicological evaluation of substituted dicyclopentadienyliron (ferrocene) compounds. Toxicol Lett 1987; 38(1– 2): 103– 108.

3. Latunde-Dada GO. Ferroptosis: role of lipid peroxidation, iron and ferritinophagy. Biochim Biophys Acta Gen Subj 2017; 1861(8): 1893– 1900. doi: 10.1016/ j.bbagen.2017.05.019.

4. Beliakova TA, Leshchev LS. Use of ferroceron for the treat­ment of iron deficiency anemia. Ter Arkh 1975; 47(6): 115– 119.

5. Patra M, Gasser G. The medicinal chemistry of ferrocene and its derivatives. Nat Rev Chem 2017; 1: 66. doi: 10.1038/ s41570-017-0066.

6. Voňka P, Hrstka R. Souhrn aktuálních poznatků o úloze estrogenového receptoru α v nádorové buněčné signalizaci. Klin Onkol 2019; 32 (Suppl 3): 3S34–3S38. doi: 10.14735/amko20193S34.

7. Acevedo-Morantes CY, Meléndez E, Singh SP et al. Cytotoxicity and reactive oxygen species generated by ferrocenium and ferrocene on MCF7 and MCF10A cell lines. J Cancer Sci Ther 2012; 4: 4271– 275. doi:10.4172/ 1948-5956.1000154.

8. Vessieres A, Corbet C, Heldt JM et al. A ferrocenyl derivative of hydroxytamoxifen elicits an estrogen receptor-independent mechanism of action in breast cancer cell lines. J Inorg Biochem 2010; 104(5): 503– 511. doi: 10.1016/ j.jinorgbio­.2009.12.020.

9. Michard Q, Jaouen G, Vessieres A et al. Evaluation of cytotoxic properties of organometallic ferrocifens on melanocytes, primary and metastatic melanoma cell lines. J Inorg Biochem 2008; 102(11): 1980– 1985. doi: 10.1016/ j.jinorgbio­.2008.07.014.

10. Birmingham JM, Seyferth D, Wilkinson G. A new preparation of bis-cyclopentadienyl-metal compounds. J Am Chem Soc 1954; 76(16): 4179. doi: 10.1021/ ja01645a038.

11. Kopf H, Kopf-Maier P. Titanocene dichloride –  the first metallocene with cancerostatic activity. Angew Chem Int Ed Engl 1979; 18(6): 477– 478. doi: 10.1002/ anie.197904771.

12. Christodoulou CV, Ferry DR, Fyfe DW et al. Phase I trial of weekly schedul­ing and pharmacokinetics of titanocene dichloride in patients with advanced cancer. J Clin Oncol 1998; 16(8): 2761– 2769. doi: 10.1200/ JCO.1998.16.8.2761.

13. Korfel A, Scheulen ME, Schmoll HJ et al. Phase I clinical and pharmacokinetic study of titanocene dichloride in adults with advanced solid tumors. Clin Cancer Res 1998; 4(11): 2701– 2708.

14. Kröger N, Kleeberg UR, Mross K et al. Phase II clinical trial of titanocene dichloride in patients with metastatic breast cancer. Oncol Res Treat 2000; 23: 60– 62. doi: 10.1159/ 000027075.

15. Lummen G, Sperl­ing H, Luboldt H et al. Phase II trial of titanocene dichloride in advanced renal-cell carcinoma. Cancer Chemother Pharmacol 1998; 42(5): 415– 417. doi: 10.1007/ s002800050838.

16. Guo M, Sun H, McArdle HJ et al. Ti(IV) uptake and release by human serum transferrin and recognition of Ti(IV)-transferrin by cancer cells: understand­ing the mechanism of action of the anticancer drug titanocene dichloride. Biochemistry 2000; 39(33): 10023– 10033. doi: 10.1021/ bi000798z.

17. Harstrick A, Schmoll HJ, Sass G et al. Titanocendichloride activity in cisplatin and doxorubicin-resistant human ovarian carcinoma cell lines. Eur J Cancer 1993; 29A(7): 1000– 1002. doi: 10.1016/ s0959-8049(05)80210-2.

18. Christodoulou CV, Eliopoulos AG, Young LS et al. Anti-proliferative activity and mechanism of action of titanocene dichloride. Br J Cancer 1998; 77(12): 2088– 2097. doi: 10.1038/ bjc.1998.352.

19. Weber H, Claffey J, Hogan M et al. Analyses of titanocenes in the spheroid-based cellular angiogenesis assay. Toxicol In Vitro 2008; 22(2): 531– 534. doi: 10.1016/ j.tiv.2007.09.014.

20. Kolberg HC, Villena-Heinsen C, Deml MM et al. Relationship between chemother­apy with paclitaxel, cisplatin, vinorelbine and titanocene dichloride and expression of proliferation markers and tumour suppressor gene p53 in human ovarian cancer xenografts in nude mice. Eur J Gynaecol Oncol 2005; 26(4): 398– 402.

21. Boyles JR, Bair MC, Campl­ing BG et al. Enhanced anti-cancer activities of some derivatives of titanocene dichloride. J Inorg Biochem 2001; 84(1– 2): 159– 162.

22. Tacke M, Allen LT, Cuffe LP et al. Novel titanocene anti-cancer drugs derived from fulvenes and titanium dichloride. J Organomet Chem 2004; 689(13): 2242– 2249. doi: 10.1016/ j.jorganchem.2004.04.015.

23. Allen OR, Croll L, Gott AL et al. Functionalized cyclopentadienyl titanium organometallic compounds as new antitumor drugs. Organometallics 2004; 23(2): 288– 292. doi: 10.1021/ om030403i.

24. McGowan MA, McGowan PC. A one-step synthesis of protected functionalised titanocene dichlorides. Inorg Chem Commun 2000; 3(7): 337– 340.

25. Potter GD, Baird MC, Cole SPC. A new series of titanocene dichloride derivatives bear­ing chiral alkylammonium groups: assessment of their cytotoxic properties. Inorg Chim Acta 2010; 364(1): 16– 22.

26. Sweeney NJ, Mendoza O, Müller-Bunz H et al. Novel benzyl substituted titanocene anti-cancer drugs. J Organomet Chem 2005; 690(21– 22): 4537– 4544. doi: 10.1016/ j.jorganchem.2005.06.039.

27. Fichtner I, Pampillon C, Sweeney NJ et al. Anti-tumor activity of titanocene Y in xenografted Caki-1 tumors in mice. Anticancer Drugs 2006; 17(3): 333– 336.

28. Bannon JH, Fichtner I, O’Neill A et al. Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo. Br J Cancer 2007; 97(9): 1234– 1241. doi: 10.1038/ sj.bjc.6604021.

29. Beckhove P, Oberschmidt O, Hanauske AR et al. Antitumor activity of titanocene Y against freshly explanted human breast tumor cells and in xenografted MCF-7 tumors in mice. Anticancer Drugs 2007; 18(3): 311– 315. doi: 10.1097/ CAD.0b013e328010a6f7.

30. Kater L, Claffey J, Hogan M et al. The role of the intrinsic FAS pathway in titanocene Y apoptosis: the mechanism of overcom­ing multiple drug resistance in malignant leukemia cells. Toxicol In Vitro 2012; 26(1): 119– 124. doi: 10.1016/ j.tiv.2011.09.010.

31. Juo P, Woo MS, Kuo CJ et al. FADD is required for multiple signal­ing events downstream of the receptor Fas. Cell Growth Differ 1999; 10(12): 797– 804.

32. Claffey J, Hogan M, Muller-Bunz H et al. Oxali-titanocene Y: a potent anticancer drug. Chem Med Chem 2008; 3(5): 729– 731. doi: 10.1002/ cmdc.200700302.

33. Fichtner I, Behrens D, Claffey J et al. Antitumor activity of oxali-titanocene Y in xenografted CAKI-1 tumors in mice. Letters in Drug Design & Discovery 2008; 5(8): 489– 493. doi: 10.2174/ 157018008786898545.

34. Deally A, Hackenberg F, Lally G et al. Synthesis and bio­logical evaluation of achiral indole-substituted titanocene dichloride derivatives. Int J Med Chem 2012; 2012: 905981. doi: 10.1155/ 2012/ 905981.

35. Walther W, Fichtner I, Deally A et al. The activity of titanocene T against xenografted Caki-1 tumors. Letters in Drug Design & Discovery 2013; 10(5): 375– 381. doi: 10.2174/ 1570180811310050002.

36. Tacke M, Cuffe LP, Gallagher WM et al. Methoxy-phenyl substituted ansa-titanocenes as potential anti-cancer drugs derived from fulvenes and titanium dichloride. J Inorg Biochem 2004; 98(12): 1987– 1994. doi: 10.1016/ j.jinorgbio­.2004.09.001.

37. Valadares MC, Ramos AL, Rehmann FJ et al. Antitumour activity of [1,2-di(cyclopentadienyl)-1,2-di(p-N,N-dimethylaminophenyl)-ethanediyl] titanium dichloride in xenografted Ehrlich‘s ascites tumour. Eur J Pharmacol 2006; 534(1– 3): 264– 270. doi: 10.1016/ j.ejphar.2006.01.056.

38. Fernandez-Gallardo J, Elie BT, Sadhukha T et al. Heterometallic titanium– gold complexes inhibit renal cancer cells in vitro and in vivo. Chem Sci 2015; 6(9): 5269– 5283. doi: 10.1039/ C5SC01753J.

39. Fernandez-Gallardo J, Elie BT, Sulzmaier FJ et al. Organometallic titanocene-gold compounds as potential chemotherapeutics in renal cancer. Study of their protein kinase inhibitory properties. Organometallics 2014; 33(22): 6669– 6681. doi: 10.1021/ om500965k.

40. Mui YF, Fernandez-Gallardo J, Elie BT et al. Titanocene-gold complexes contain­ing N-heterocyclic carbene ligands inhibit growth of prostate, renal, and colon cancers in vitro. Organometallics 2016; 35(9): 1218– 1227. doi: 10.1021/ acs.organomet.6b00051.

41. Keppler BK, Heim ME, Flechtner H et al. Assessment of the preclinical activity of budotitane in three different transplantable tumor systems, its lack of mutagenicity, and first results of clinical phase I studies. Arzneimittelforschung 1989; 39(6): 706– 709.

42. Keppler BK, Schmahl D. Preclinical evaluation of dichlorobis(1-phenylbutane-1,3-dionato)titanium (IV) and budotitane. Two representatives of the new class of antitumor-active bis-beta-diketonato metal complexes. Arzneimittelforschung 1986; 36(12): 1822– 1828.

43. Schill­ing T, Keppler KB, Heim ME et al. Clinical phase I and pharmacokinetic trial of the new titanium complex budotitane. Invest New Drugs 1996; 13(4): 327– 332.

44. Qian ZM, Li H, Sun H et al. Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacol Rev 2002; 54(4): 561– 587.

45. Aarabi MH, Mirhashemi SM, Ani M et al. Comparative bind­ing studies of titanium and iron to human serum transferrin. Asian J Biochem 2011; 6(2): 191– 199. doi: 10.3923/ ajb.2011.191.199.

46. Lally G, Deally A, Hackenberg F et al. Titanocene Y - transport and target­ing of an anticancer drug candidate. Letters in Drug Design & Discovery 2013; 10(8): 675– 682. doi: 10.2174/ 15701808113100890027.

47. Pavlaki M, Debeli K, Triantaphyllidou IE et al. A proposed mechanism for the inhibitory effect of the anticancer agent titanocene dichloride on tumour gelatinases and other proteolytic enzymes. J Biol Inorg Chem 2009; 14(6): 947– 957. doi: 10.1007/ s00775-009-0507-7.

48. Tinoco AD, Eames EV, Valentine AM. Reconsideration of serum Ti(IV) transport: albumin and transferrin traffick­ing of Ti(IV) and its complexes. J Am Chem Soc 2008; 130(7): 2262– 2270. doi: doi: 10.1021/ ja076364+.

49. Gasser G, Ott I, Metzler-Nolte N. Organometallic anticancer compounds. J Med Chem 2011; 54(1): 3– 25. doi: 10.1021/ jm100020w.

50. Berger MR, Garzon FT, Keppler BK et al. Efficacy of new ruthenium complexes against chemically induced autochthonous colorectal carcinoma in rats. Anticancer Res 1989; 9(3): 761– 765.

51. Dale LD, Tocher JH, Dyson TM et al. Studies on DNA damage and induction of SOS repair by novel multifunctional bio­reducible compounds. II. A metronidazole adduct of a ruthenium-arene compound. Anticancer Drug Des 1992; 7(1): 3– 14.

52. Canovic P, Simovic AR, Radisavljevic S et al. Impact of aromaticity on anticancer activity of polypyridyl ruthenium(II) complexes: synthesis, structure, DNA/ protein binding, lipophilicity and anticancer activity. J Biol Inorg Chem 2017; 22(7): 1007– 1028. doi: 10.1007/ s00775-017-1479-7.

53. Castonguay A, Doucet C, Juhas M et al. New ruthenium(II)-letrozole complexes as anticancer therapeutics. J Med Chem 2012; 55(20): 8799– 8806. doi: 10.1021/ jm301103y.

54. Gossens C, Tavernelli I, Rothlisberger U. Structural and energetic properties of organometallic ruthenium(II) diamine anticancer compounds and their interaction with nucleobases. J Chem Theory Comput 2007; 3(3): 1212– 1222. doi: 10.1021/ ct6003577.

55. Chelopo MP, Pawar SA, Sokhela MK et al. Anticancer activity of ruthenium(II) arene complexes bear­ing 1,2,3,4-tetrahydroisoquinoline amino alcohol ligands. Eur J Med Chem 2013; 66407– 66414. doi: 10.1016/ j.ejmech.2013.05.048.

56. Nowak-Sliwinska P, van Beijnum JR, Casini A et al. Organometallic ruthenium(II) arene compounds with antiangiogenic activity. J Med Chem 2011; 54(11): 3895– 3902. doi: 10.1021/ jm2002074.

57. Sava G, Clerici K, Capozzi I et al. Reduction of lung metastasis by ImH[trans-RuCl4(DMSO)Im]: mechanism of the selective action investigated on mouse tumors. Anticancer Drugs 1999; 10(1): 129– 138.

58. Weiss A, Berndsen RH, Dubois M et al. In vivo anti-tumor activity of the organometallic ruthenium(II)-arene complex [Ru(h6-p-cymene)-Cl2(pta)] (RAPTA-C) in human ovarian and colorectal carcinomas. Chem Sci 2014; 12(5): 4742– 4748.

59. Bergamo A, Zorzet S, Gava B et al. Effects of NAMI-Aand some related ruthenium complexes on cell viability after short exposure of tumor cells. Anticancer Drugs 2000; 11(8): 665– 672.

60. Debidda M, Sanna B, Cossu A et al. NAMI-A inhibits the PMA-induced ODC gene expression in ECV304 cells: involvement of PKC/ Raf/ Mek/ ERK signall­ing pathway. Int J Oncol 2003; 23(2): 477– 482.

61. Sava G, Capozzi I, Clerici K et al. Pharmacological control of lung metastases of solid tumours by a novel ruthenium complex. Clin Exp Metastasis 1998; 16(4): 371– 379.

62. Sava G, Bergamo A, Zorzet S et al. Influence of chemical stability on the activity of the antimetastasis ruthenium compound NAMI-A. Eur J Cancer 2002; 38(3): 427– 435. doi: 10.1016/ s0959-8049(01)00389-6.

63. Sava G, Zorzet S, Turrin C et al. Dual action of NAMI-A in inhibition of solid tumor metastasis: selective target­ing of metastatic cells and bind­ing to collagen. Clin Cancer Res 2003; 9(5): 1898– 1905.

64. Vacca A, Bruno M, Boccarelli A et al. Inhibition of endothelial cell functions and of angiogenesis by the metastasis inhibitor NAMI-A. Br J Cancer 2002; 86(6): 993– 998. doi: 10.1038/ sj.bjc.6600176.

65. Morbidelli L, Donnini S, Filippi S et al. Antiangiogenic properties of selected ruthenium(III) complexes that are nitric oxide scavengers. Br J Cancer 2003; 88(9): 1484– 1491. doi: 10.1038/ sj.bjc.6600906.

66. Pacor S, Zorzet S, Cocchietto M et al. Intratumoral NAMI-A treatment triggers metastasis reduction, which correlates to CD44 regulation and tumor infiltrat­ing lymphocyte recruitment. J Pharmacol Exp Ther 2004; 310(2): 737– 744. doi: 10.1124/ jpet.104.066175.

67. Bacac M, Hotze AC, van der Schilden K et al. The hydrolysis of the anti-cancer ruthenium complex NAMI-A affects its DNA bind­ing and antimetastatic activity: an NMR evaluation. J Inorg Biochem 2004; 98(2): 402– 412.

68. Rademaker-Lakhai JM, van den Bongard D, Pluim D et al. A phase I and pharmacological study with imidazolium-trans-DMSO-imidazole-tetrachlororuthenate, a novel ruthenium anticancer agent. Clin Cancer Res 2004; 10(11): 3717– 3727. doi: 10.1158/ 1078-0432.CCR-03-0746.

69. Leijen S, Burgers SA, Baas P et al. Phase I/ II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line ther­apy. Invest New Drugs 2015; 33(1): 201– 214. doi: 10.1007/ s10637-014-0179-1.

70. Seelig MH, Berger MR, Keppler BK. Antineoplastic activity of three ruthenium derivatives against chemically induced colorectal carcinoma in rats. J Cancer Res Clin Oncol 1992; 118(3): 195– 200.

71. Heffeter P, Pongratz M, Steiner E et al. Intrinsic and acquired forms of resistance against the anticancer ruthenium compound KP1019 [indazolium trans-[tetrachlorobis(1H-indazole)ruthenate (III)] (FFC14A). J Pharmacol Exp Ther 2005; 312(1): 281– 289. doi: 10.1124/ jpet.104.073395.

72. Hartinger CG, Jakupec MA, Zorbas-Seifried S et al. KP1019, a new redox-active anticancer agent – preclinical development and results of a clinical phase I study in tumor patients. Chem Biodivers 2008; 5(10): 2140– 2155. doi: 10.1002/ cbdv.200890195.

73. Stevens SK, Strehle AP, Miller RL et al. The anticancer ruthenium complex KP1019 induces DNA damage, lead­ing to cell cycle delay and cell death in Saccharomyces cerevisiae. Mol Pharmacol 2013; 83(1): 225– 234. doi: 10.1124/ mol.112.079657.

74. Hartinger CG, Zorbas-Seifried S, Jakupec MA et al. From bench to bedside – preclinical and early clinical development of the anticancer agent indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019 or FFC14A). J Inorg Biochem 2006; 100(5– 6): 891– 904. doi: 10.1016/ j.jinorgbio­.2006.02.013.

75. Lentz F, Drescher A, Lindauer A et al. Pharmacokinetics of a novel anticancer ruthenium complex (KP1019, FFC14A) in a phase I dose-escalation study. Anticancer Drugs 2009; 20(2): 97– 103. doi: 10.1097/ CAD.0b013e328322fbc5.

76. Peti W, Pieper T, Sommer M et al. Synthesis of tumor-inhibit­ing complex salts contain­ing the anion trans-tetrachlorobis(indazole)ruthenate(III) and crystal structure of the tetraphenylphosphonium salt. Eur J Inorg Chem 1999; 1999(9): 1551– 1555.

77. Kratz F, Hartmann M, Keppler B et al. The bind­ing pro­p­-erties of two antitumor ruthenium(III) complexes to apotransferrin. J Biol Chem 1994; 269(4): 2581– 2588.

78. Heffeter P, Atil B, Kryeziu K et al. The ruthenium compound KP1339 potentiates the anticancer activity of sorafenib in vitro and in vivo. Eur J Cancer 2013; 49(15): 3366– 3375. doi: 10.1016/ j.ejca.2013.05.018.

79. Dickson NR, Jones SF, Burris HA et al. A phase I dose-escalation study of NKP-1339 in patients with advanced solid tumors refractory to treatment. J Clin Oncol 2011; 29 (Suppl): abstr. 2607.

80. Burris HA, Bakewell S, Bendell JC et al. Safety and activity of IT-139, a ruthenium-based compound, in patients with advanced solid tumours: a first-in-human, open-label, dose-escalation phase I study with expansion cohort. ESMO Open 2016; 1(6): e000154. doi: 10.1136/ esmoopen-2016-000154.

81. Lizardo MM, Morrow JJ, Miller TE et al. Upregulation of glucose-regulated protein 78 in metastatic cancer cells is necessary for lung metastasis progression. Neoplasia 2016; 18(11): 699– 710. doi: 10.1016/ j.neo.2016.09.001.

82. Gifford JB, Huang W, Zeleniak AE et al. Expression of GRP78, master regulator of the unfolded protein response, increases chemoresistance in pancreatic ductal adenocarcinoma. Mol Cancer Ther 2016; 15(5): 1043– 1052. doi: 10.1158/ 1535-7163.MCT-15-0774.

83. Flocke LS, Trondl R, Jakupec MA et al. Molecular mode of action of NKP-1339 - a clinically investigated ruthenium-based drug –  involves ER- and ROS-related effects in colon carcinoma cell lines. Invest New Drugs 2016; 34(3): 261– 268. doi: 10.1007/ s10637-016-0337-8.

84. Bergamo A, Masi A, Dyson PJ et al. Modulation of the metastatic progression of breast cancer with an organometallic ruthenium compound. Int J Oncol 2008; 33(6): 1281– 1289.

85. Scolaro C, Bergamo A, Brescacin L et al. In vitro and in vivo evaluation of ruthenium(II)-arene PTA complexes. J Med Chem 2005; 48(12): 4161– 4171. doi: 10.1021/ jm050015d.

86. Chatterjee S, Kundu S, Bhattacharyya A et al. The ruthenium(II)-arene compound RAPTA-C induces apoptosis in EAC cells through mitochondrial and p53-JNK pathways. J Biol Inorg Chem 2008; 13(7): 1149– 1155. doi: 10.1007/ s00775-008-0400-9.

87. Lu H, Blunden BM, Scarano W et al. Anti-metastatic effects of RAPTA-C conjugated polymeric micelles on two-dimensional (2D) breast tumor cells and three-dimensional (3D) multicellular tumor spheroids. Acta Biomater 2016; 3268– 3276. doi: 10.1016/ j.actbio­.2015.12.020.

88. Lu M, Henry CE, Lai H et al. A new 3D organotypic model of ovarian cancer to help evaluate the antimetastatic activity of RAPTA-C conjugated micelles. Biomater Sci 2019; 7(4): 1652– 1660. doi: 10.1039/ c8bm01326h.

89. Chen L, Fu C, Deng Y et al. A pH-sensitive nanocarrier for tumor targeting: delivery of ruthenium complex for tumor theranostic by pH-sensitive nanocapsule. Pharm Res 2016; 33(12): 2989– 2998. doi: 10.1007/ s11095-016-2021-2.

90. Zhang P, Huang H, Huang J et al. Noncovalent ruthenium(II) complexes-single-walled carbon nanotube composites for bimodal photothermal and photodynamic ther­apy with near-infrared irradiation. ACS Appl Mater Interfaces 2015; 7(41): 23278– 23290. doi: 10.1021/ acsami.5b07510.

91. Zhao S, Zhu X, Cao C et al. Transferrin modified ruthenium nanoparticles with good bio­compatibility for photothermal tumor ther­apy. J Colloid Interface Sci 2018; 511325– 511334. doi: 10.1016/ j.jcis.2017.10.023.

92. Wang F, Chen H, Parsons S et al. Kinetics of aquation and anation of ruthenium(II) arene anticancer complexes, acidity and X-ray structures of aqua adducts. Chemistry 2003; 9(23): 5810– 5820. doi: 10.1002/ chem.200304724.

93. Yan YK, Melchart M, Habtemariam A et al. Organometallic chemistry, bio­logy and medicine: ruthenium arene anticancer complexes. Chem Commun (Camb) 2005(38): 4764– 4776. doi: 10.1039/ b508531b.

94. Scolaro C, Chaplin AB, Hartinger CG et al. Tun­ing the hydrophobicity of ruthenium(II)-arene (RAPTA) drugs to modify uptake, bio­molecular interactions and efficacy. Dalton Trans 2007(43): 5065– 5072. doi: 10.1039/ b705449a.

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