Recent Advances in Bioconjugated Transition Metal Complexes for Cancer Therapy
Source abstract
Abstract
The introduction of biologically relevant organic moieties in the coordination sphere of transition metal complexes has recently become a well-established strategy to increase the selectivity and biocompatibility of metallodrugs. In this review, the major advances achieved in this area of research in the last three years are described in detail. Particular attention is given to the metal complexes bearing the main biomolecules of life: carbohydrates, lipids, nucleotides, proteins and vitamins. Each paragraph summarizes the synthetic strategy employed to obtain the complexes of interest as well as the most interesting biological results obtained with these potential metallodrugs. Moreover, the structure–activity relationships observed by the different research groups are described and discussed, with the goal of suggesting to the reader the ligand/metal centre combinations that provide the most promising results in the fight against cancer. Some of the compounds examined in this review as well as other bioconjugated metal complexes published in recent decades exhibit interesting selectivity towards cancer cells over normal ones and a specific mode of action. These latter aspects are the basis of what is commonly known as anticancer target therapy.
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Research context
OpenAlex topics: Metal complexes synthesis and properties · Click Chemistry and Applications · Ferrocene Chemistry and Applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca’ Foscari, Campus Scientifico, Via Torino 155, 30174 Venezia-Mestre, Italy
Dipartimento di Scienze Chimiche, Università degli Studi di Padova, Via Marzolo 1, 35131 Padova, Italy
References (100+)
Show source-provided references
1. Across the Spectrum: Integrating Multidimensional Metal Analytics for In Situ Metallomic Imaging10.1039/C8MT00235E ↗
2. Insights into Trace Metal Metabolism in Health and Disease from PET: “PET Metallomics”10.2967/jnumed.118.212803 ↗
3. Toxic Mechanisms of Five Heavy Metals: Mercury, Lead, Chromium, Cadmium, and Arsenic
4. Toxicity of Metal Compounds: Knowledge and Myths10.1021/acs.organomet.7b00605 ↗
5. Metal Complexes as Drugs and Therapeutic Agents10.1016/B978-0-08-102688-5.00018-0 ↗
6. Cisplatin: The First Metal Based Anticancer Drug10.1016/j.bioorg.2019.102925 ↗
7. Blomme Toxicology Strategies for Drug Discovery: Present and Future10.1021/acs.chemrestox.5b00407 ↗
8. Activity-Based Protein Profiling: Recent Advances in Medicinal Chemistry10.1016/j.ejmech.2020.112151 ↗
9. Ferraro, M.G., Piccolo, M., Misso, G., Santamaria, R., and Irace, C. (2022). Bioactivity and Development of Small Non-Platinum Metal-Based Chemotherapeutics. Pharmaceutics, 14.10.3390/pharmaceutics14050954 ↗
10. Stankovic, J.S.K., Selakovic, D., Mihailovic, V., and Rosic, G. (2020). Antioxidant Supplementation in the Treatment of Neurotoxicity Induced by Platinum-Based Chemotherapeutics—A Review. Int. J. Mol. Sci., 21.10.3390/ijms21207753 ↗
11. Metal- and Metalloid-Based Compounds to Target and Reverse Cancer Multidrug Resistance10.1016/j.drup.2021.100778 ↗
12. Lipoplatin Formulation Review Article10.1155/2012/581363 ↗
13. Metal Complexes in Medicine: An Overview and Update from Drug Design Perspective
14. Metallodrugs Are Unique: Opportunities and Challenges of Discovery and Development10.1039/D0SC04082G ↗
15. A Categorization of Metal Anticancer Compounds Based on Their Mode of Action10.1039/b905798f ↗
16. Stimuli-Responsive Metal Complexes for Biomedical Applications10.1002/anie.202205900 ↗
17. Phototherapeutic Anticancer Strategies with First-Row Transition Metal Complexes: A Critical Review10.1039/D1CS00609F ↗
18. Features of Third Generation Photosensitizers Used in Anticancer Photodynamic Therapy: Review10.1016/j.pdpdt.2020.102091 ↗
19. Recent Development of Photofunctional Transition Metal−Peptide Conjugates for Bioimaging and Therapeutic Applications10.1002/ejic.202200455 ↗
20. Metal Complexes for Catalytic and Photocatalytic Reactions in Living Cells and Organisms10.1039/D2SC05672K ↗
21. Controlled In-Cell Generation of Active Palladium(0) Species for Bioorthogonal Decaging10.1002/ange.202113519 ↗
22. Classification of Metal-Based Drugs According to Their Mechanisms of Action10.1016/j.chempr.2019.10.013 ↗
23. Bioorthogonal Strategies for the In Vivo Synthesis or Release of Drugs10.1016/j.bmc.2021.116310 ↗
24. Organometallic Catalysis in Biological Media and Living Settings10.1016/j.ccr.2018.01.011 ↗
25. In Vivo Catalyzed New-to-Nature Reactions10.1016/j.copbio.2017.12.008 ↗
26. In Vivo Organic Synthesis by Metal Catalysts10.1016/j.bmc.2021.116353 ↗
27. Unleashing the Power of Bond Cleavage Chemistry in Living Systems10.1021/acscentsci.1c00124 ↗
28. Transfer Hydrogenation Catalysis in Cells as a New Approach to Anticancer Drug Design10.1038/ncomms7582 ↗
29. Tools and Methods for Investigating Synthetic Metal-Catalyzed Reactions in Living Cells10.1021/acscatal.1c00438 ↗
30. Transition Metal-Promoted Reactions in Aqueous Media and Biological Settings10.1002/chem.202003927 ↗
31. Giorgi, E., Binacchi, F., Marotta, C., Cirri, D., Gabbiani, C., Hangan, C., Lucaciu, R.L., Giorgi, E., Binacchi, F., and Marotta, C. (2022). Highlights of New Strategies to Increase the Efficacy of Transition Metal Complexes for Cancer Treatments. Molecules, 28.10.3390/molecules28010273 ↗
32. Metal Complexes in Target-Specific Anticancer Therapy: Recent Trends and Challenges10.1155/2022/9261683 ↗
33. Latest Developments in Metal Complexes as Anticancer Agents10.1016/j.ccr.2021.214307 ↗
34. Natural Products in Drug Discovery: Advances and Opportunities10.1038/s41573-020-00114-z ↗
35. A New Hybrid Ligand and Its Metal Complexes from a Natural Plant (Styrax officinalis) Bearing Egonol, Thiosemicarbazone and Oxime Units, and Their Anti-Cancer Activities10.1002/aoc.6784 ↗
36. Synthesis of New Allyl Palladium Complexes Bearing Purine-Based NHC Ligands with Antiproliferative and Proapoptotic Activities on Human Ovarian Cancer Cell Lines10.1039/C8DT01831F ↗
37. Palladacyclopentadienyl Complexes Bearing Purine-Based N-Heterocyclic Carbenes: A New Class of Promising Antiproliferative Agents against Human Ovarian Cancer10.1002/aoc.4902 ↗
38. Palladium (0) Olefin Complexes Bearing Purine-Based N-Heterocyclic Carbenes and 1,3,5-Triaza-7-Phosphaadamantane (PTA): Synthesis, Characterization and Antiproliferative Activity toward Human Ovarian Cancer Cell Lines10.1016/j.jorganchem.2019.07.008 ↗
39. A Mini-Review: Recent Advances in Coumarin-Metal Complexes with Biological Properties10.3389/fchem.2021.781779 ↗
40. Fluorescent Dyes in Organometallic Chemistry: Coumarin-Tagged NHC–Metal Complexes10.1002/ejic.201800395 ↗
41. Patil, S.A., Kandathil, V., Sobha, A., Somappa, S.B., Feldman, M.R., Bugarin, A., and Patil, S.A. (2022). Comprehensive Review on Medicinal Applications of Coumarin-Derived Imine–Metal Complexes. Molecules, 27.10.3390/molecules27165220 ↗
42. Metal-Polyphenol Complexes as Versatile Building Blocks for Functional Biomaterials10.1007/s12257-021-0022-4 ↗
43. Ma, D.L., Wu, C., Cheng, S.S., Lee, F.W., Han, Q.B., and Leung, C.H. (2019). Development of Natural Product-Conjugated Metal Complexes as Cancer Therapies. Int. J. Mol. Sci., 20.10.3390/ijms20020341 ↗
44. Metal Complexes of Natural Product Like-Compounds with Antitumor Activity10.2174/1871520618666180420165821 ↗
45. The Warburg Effect: How Does It Benefit Cancer Cells?10.1016/j.tibs.2015.12.001 ↗
46. The Mechanism of Warburg Effect-Induced Chemoresistance in Cancer
47. Carbohydrates: Potential Sweet Tools Against Cancer10.2174/0929867325666180719114150 ↗
48. Glycoconjugated Metal Complexes as Cancer Diagnostic and Therapeutic Agents10.1002/cmdc.202000456 ↗
49. A Hydrophilic Olefin Pt(0) Complex Containing a Glucoconjugated 2-Iminopyridine Ligand: Synthesis, Characterization, Stereochemistry and Biological Activity10.1016/j.ica.2020.120092 ↗
50. Five-Coordinate Platinum(II) Compounds as Potential Anticancer Agents10.1002/ejic.201900771 ↗
51. Pt(II) versus Pt(IV) in Carbene Glycoconjugate Antitumor Agents: Minimal Structural Variations and Great Performance Changes10.1021/acs.inorgchem.9b03683 ↗
52. The Beauty of Gold: Knowledge of Mechanisms Leads to Different Applications of Organogold Compounds in Medicine and Catalysis10.1246/cl.210238 ↗
53. Thioredoxin Reductase: A Target for Gold Compounds Acting as Potential Anticancer Drugs10.1016/j.ccr.2009.02.026 ↗
54. Interactions of Selected Gold(III) Complexes with DNA G Quadruplexes10.1039/C4DT02698E ↗
55. G-Quadruplexes On the Mechanism of Gold/NHC Compounds Binding to DNAG-Quadruplexes:Combined Metadynamics and Biophysical Methods10.1002/ange.201805727 ↗
56. Dinuclear Gold(I) Complexes: From Bonding to Applications10.1039/D0CS00438C ↗
57. Halo Complexes of Gold(I) Containing Glycoconjugate Carbene Ligands: Synthesis, Characterization, Cytotoxicity and Interaction with Proteins and DNA Model Systems10.1039/D2DT00423B ↗
58. Tresin, F., Stoppa, V., Baron, M., Biffis, A., Annunziata, A., D’Elia, L., Monti, D.M., Ruffo, F., Roverso, M., and Sgarbossa, P. (2020). Synthesis and Biological Studies on Dinuclear Gold(I) Complexes with Di-(N-Heterocyclic Carbene) Ligands Functionalized with Carbohydrates. Molecules, 25.10.3390/molecules25173850 ↗
59. Synthetic Routes to Late Transition Metal–NHC Complexes10.1016/j.trechm.2020.06.001 ↗
60. Straightforward Synthetic Route to Gold(I)-Thiolato Glycoconjugate Complexes Bearing NHC Ligands (NHC = N-Heterocyclic Carbene) and Their Promising Anticancer Activity10.1039/D1NJ02117F ↗
61. Azoliums and Ag(I)-N-Heterocyclic Carbene Thioglycosides: Synthesis, Reactivity and Bioactivity10.1002/ejoc.202101499 ↗
62. Anti-Cancer Palladium Complexes: A Focus on PdX2L2, Palladacycles and Related Complexes10.1039/C4CS00063C ↗
63. A Critical Review of Palladium Organometallic Anticancer Agents10.1016/j.xcrp.2021.100446 ↗
64. Indenyl and Allyl Palladate Complexes Bearing N-Heterocyclic Carbene Ligands: An Easily Accessible Class of New Anticancer Drug Candidates
65. The Anticancer Activity of an Air-Stable Pd(I)-NHC (NHC = N-Heterocyclic Carbene) Dimer10.1039/D0CC03883K ↗
66. Palladium(II)-H3-Allyl Complexes Bearing N-Trifluoromethyl N-Heterocyclic Carbenes: A New Generation of Anticancer Agents That Restrain the Growth of High-Grade Serous Ovarian Cancer Tumoroids10.1002/chem.202002199 ↗
67. Allyl Palladium Complexes Bearing Carbohydrate-Based N-Heterocyclic Carbenes: Anticancer Agents for Selective and Potent In Vitro Cytotoxicity10.1002/aoc.5876 ↗
68. New Glycoconjugation Strategies for Ruthenium(II) Arene Complexes via Phosphane Ligands and Assessment of Their Antiproliferative Activity10.1016/j.bioorg.2022.105901 ↗
69. Kacsir, I., Sipos, A., Ujlaki, G., Buglyó, P., Somsák, L., Bai, P., and Bokor, É. (2021). Ruthenium Half-Sandwich Type Complexes with Bidentate Monosaccharide Ligands Show Antineoplastic Activity in Ovarian Cancer Cell Models through Reactive Oxygen Species Production. Int. J. Mol. Sci., 22.10.3390/ijms221910454 ↗
70. Kacsir, I., Sipos, A., Bényei, A., Janka, E., Buglyó, P., Somsák, L., Bai, P., and Bokor, É. (2022). Reactive Oxygen Species Production Is Responsible for Antineoplastic Activity of Osmium, Ruthenium, Iridium and Rhodium Half-Sandwich Type Complexes with Bidentate Glycosyl Heterocyclic Ligands in Various Cancer Cell Models. Int. J. Mol. Sci., 23.10.3390/ijms23020813 ↗
71. Tethering Carbohydrates to the Vinyliminium Ligand of Antiproliferative Organometallic Diiron Complexes10.1021/acs.organomet.1c00519 ↗
72. Neutral Re(I) Complex Platform for Live Intracellular Imaging10.1021/acs.inorgchem.1c00418 ↗
73. Recent Advances in Peptide-Based Approaches for Cancer Treatment10.2174/0929867325666171123204851 ↗
74. Considerations for the Design of Antibody-Based Therapeutics10.1016/j.xphs.2019.05.031 ↗
75. Antibody−Drug Conjugates for Immunology
76. The Interaction of Rhodium Compounds with Proteins: A Structural Overview10.1016/j.ccr.2021.213999 ↗
77. Bolzati, C., and Spolaore, B. (2021). Enzymatic Methods for the Site-Specific Radiolabeling of Targeting Proteins. Molecules, 26.10.3390/molecules26123492 ↗
78. Metal-Based Antibody Drug Conjugates. Potential and Challenges in Their Application as Targeted Therapies in Cancer10.1016/j.jinorgbio.2019.110780 ↗
79. To View Your Biomolecule, Click inside the Cell10.1002/anie.202101502 ↗
80. Metal-Mediated Functionalization of Natural Peptides and Proteins: Panning for Bioconjugation Gold10.1002/anie.201807536 ↗
81. Nanobodies: Next Generation of Cancer Diagnostics and Therapeutics10.3389/fonc.2020.01182 ↗
82. Gayraud, F., Klußmann, M., and Neundorf, I. (2021). Recent Advances and Trends in Chemical Cpp–Drug Conjugation Techniques. Molecules, 26.10.3390/molecules26061591 ↗
83. Lomis, N., Westfall, S., Farahdel, L., Malhotra, M., Shum-Tim, D., and Prakash, S. (2016). Human Serum Albumin Nanoparticles for Use in Cancer Drug Delivery: Process Optimization and In Vitro Characterization. Nanomaterials, 6.10.3390/nano6060116 ↗
84. Design Strategies and Medicinal Applications of Metal-Peptidic Bioconjugates 30th Anniversary Review10.1021/acs.bioconjchem.0c00152 ↗
85. Facile Protein Conjugation of Platinum for Light-Activated Cytotoxic Payload Release10.1039/D1CC02722K ↗
86. Synthetic Therapeutic Peptides: Science and Market10.1016/j.drudis.2009.10.009 ↗
87. A Mini-Review and Perspective on Multicyclic Peptide Mimics of Antibodies10.1016/j.cclet.2018.03.015 ↗
88. Synthesis and DNA Interaction Studies of Ru(II) Cell Penetrating Peptide (CPP) Bioconjugates10.1039/D1DT01776D ↗
89. Towards Selective Delivery of a Ruthenium(II) Polypyridyl Complex-Containing Bombesin Conjugate into Cancer Cells10.1002/cbic.202200647 ↗
90. Synthesis and Characterization of an Epidermal Growth Factor Receptor-Selective RuII Polypyridyl–Nanobody Conjugate as a Photosensitizer for Photodynamic Therapy10.1002/cbic.201900419 ↗
91. In Situ Prodrug Activation by an Affibody-Ruthenium Catalyst Hybrid for HER2-Targeted Chemotherapy10.1002/anie.202202855 ↗
92. Synthesis and Biological Evaluation of Metallocene-Tethered Peptidyl Inhibitors of CDC2510.1021/acs.organomet.1c00345 ↗
93. Bifunctional Chelators for Radiorhenium: Past, Present and Future Outlook10.1039/D1MD00364J ↗
94. Successful Application of CuAAC Click Reaction in Constructing 64Cu-Labeled Antibody Conjugates for Immuno-PET Imaging10.1021/acsabm.0c01555 ↗
95. Bioconjugate Supramolecular Pd2+ Metallacages Penetrate the Blood Brain Barrier In Vitro and In Vivo10.1021/acs.bioconjchem.0c00659 ↗
96. Development and Preclinical Evaluation of 99m Tc-and 186 Re-Labeled NOTA and NODAGA Bioconjugates Demonstrating Matched Pair Targeting of GRPR-Expressing Tumors10.1007/s11307-020-01537-1 ↗
97. Direct Labeling of a Somatostatin Receptor Antagonist via Peptide Cyclization with Re, 99mTc and 186Re Metal Centers: Radiochemistry and in Vitro Evaluation10.1016/j.nucmedbio.2020.12.007 ↗
98. Markovic, M., Ben-Shabat, S., Aponick, A., Zimmermann, E.M., and Dahan, A. (2020). Lipids and Lipid-Processing Pathways in Drug Delivery and Therapeutics. Int. J. Mol. Sci., 21.10.3390/ijms21093248 ↗
99. Anti-Tumor Activities of Lipids and Lipid Analogues and Their Development as Potential Anticancer Drugs10.1016/j.pharmthera.2015.01.008 ↗
100. Majumder, J., and Minko, T. (2021). Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and Sirna for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and Egfr Mutations. Pharmaceutics, 13.10.3390/pharmaceutics13071063 ↗