Third row transition metals for the treatment of cancer

Johnstone, Timothy C.; Suntharalingam, Kogularamanan; Lippard, Stephen J.

doi:10.1098/rsta.2014.0185

Cited by 102 publications

(101 citation statements)

References 47 publications

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“…8 It crosslinks with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA damage, and subsequently inducing apoptosis in cancer cells. [9][10][11] Hydroxyapatite (HAp) is the major component of the human bone structure with chemical formula Ca 10 (PO 4 ) 6 (OH) 2 . The properties of porous surfaces have been investigated as delivery carriers for a variety of pharmaceutical molecules.…”

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confidence: 99%

Electrochemical Deposition of Cisplatin on Pure Magnesium

Lai

Lin

Hsu

et al. 2018

J. Electrochem. Soc.

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In this research, the cisplatin has been successfully deposited on pure Mg specimen, degradable and promising for the tumor treatment by its local sustained release to prevent the cancer from metastasis and even to achieve its apoptosis. The cathodic polarization tests coupled with electrochemical reactions in various concentrations of cisplatin solutions were qualitatively and quantitatively analyzed to speculate the deposition mechanism of cisplatin by UV visible spectrometer, Fourier transform infrared spectroscopy, field emission scanning electron microscope coupled with energy-dispersive spectroscopy, focused ion beam, and X-ray diffractometer. The drug, cisplatin, is deposited on the pure Mg through exchanging Cl − with OH − , produced by the electrochemical method, to form strong hydrogen bonds for attracting one another. The FESEM images of cisplatin coated Mg specimens reveal that the diameter of cisplatin particle is around 50-150 nm with sphere-like shape. While that on cisplatin/HAp composite is less than 30 nm. Due to the high porosity, the drug loading on cisplatin/HAp coated one can be enhanced from 34.65 to 84.93 μg/cm 2 . Also, the drug release duration can be elongated from one day burst to 3 weeks sustained release, which is promising for future clinical applications. There are many ways to treat cancer, including surgery, chemotherapy, radiotherapy, targeted therapy and so on. Among all these therapeutic methods, the conventional drug administration method, chemotherapy, is an indispensable choice for its high efficiency. Though widely utilized, it causes severe complications. In fact, chemotherapy affects people systemically, which kills not only tumor cells but also normal cells like immune cells. In many situations, people can't help but stop chemotherapy treatment before cancer cells eradicated due to severe side effects including mouth sores, hypersensitivity reactions, nausea, vomiting, diarrhea, low blood counts and hair loss.1 Current development of carriers to release drugs locally at controlled rate, which are more specific and safe due to dramatic reducing the side effects, are interesting and spotlighted. 2-5Over the last 40 years, platinum-based drugs become the significant medicines for cancer therapy, approximately half of cancer patients undergo platinum-based drugs chemotherapeutic treatment. Cisplatin and carboplatin are two major platinum-based drugs used in chemotherapy.5 Cis-diamminedichloroplatinum (II) (CDDP), commonly called cisplatin, is the first anticancer drug, which was discovered in 1965 and approved for clinical use in 1978. 6 It is the preferred medicine for a variety of solid tumors, such as testicular and ovarian cancers, and is also used for treating bladder, cervical, esophageal, and small cell lung cancer. The success in cisplatin-based chemotherapy drugs strongly depends on how careful the drug's dosages are monitored in order to reduce severe side-effects. 5,7 This show how important the localized cancer treatment is through sustaining drug release, ac...

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confidence: 99%

Electrochemical Deposition of Cisplatin on Pure Magnesium

Lai

Lin

Hsu

et al. 2018

J. Electrochem. Soc.

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“…The synthesis of the multitudes of experiments and trials conducted by chemists, biologists, and physicians has produced a consistent framework under which we can explain the data that have been obtained from compounds analogous to cisplatin. 14,15 The analogy extends to include those platinum complexes that are neutral and square-planar with cis am(m)ine ligands and cis anionic ligands. The am(m)ine ligands can be chelating or non-chelating and are referred to as the “nonleaving group ligands” because, as described below, they remain bound to the metal center throughout the course of the mechanism.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…The generalized mechanism of action involves four key steps (Figure 3): (i) cellular uptake, (ii) aquation/activation, (iii) DNA binding, and (iv) cellular processing of DNA lesions leading to apoptosis. 15 …”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…Because of the steric restraints imposed by the DNA double helix, it seemed unlikely that DNA cross-linking of the cisplatin type was operative, 15 although modelling studies suggest that such adducts may be able to form. 379 Monofunctional adducts could also conceivably form, 380,381 but the generally slow kinetics of ligand substitution at platinum(IV) argue against this process being of great biological relevance.…”

Section: Platinum(iv) Complexes With Non-cisplatin-like Mechanismsmentioning

confidence: 99%

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The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs

2016

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The platinum drugs, cisplatin, carboplatin, and oxaliplatin, prevail in the treatment of cancer,, but new platinum agents have been very slow to enter the clinic. Recently, however, there has been a surge of activity, based on a great deal of mechanistic information, aimed at developing non-classical platinum complexes that operate via mechanisms of action distinct from those of the approved drugs. The use of nanodelivery devices has also grown and many different strategies have been explored to incorporate platinum warheads into nanomedicine constructs. In this review, we discuss these efforts to create the next generation of platinum anticancer drugs. The introduction provides the reader with a brief overview of the use, development, and mechanism of action of the approved platinum drugs to provide the context in which more recent research has flourished. We then describe approaches that explore non-classical platinum(II) complexes with trans geometry and with a monofunctional coordination mode, polynuclear platinum(II) compounds, platinum(IV) prodrugs, dual-treat agents, and photoactivatable platinum(IV) complexes. Nanodelivery particles designed to deliver platinum(IV) complexes will also be discussed, including carbon nanotubes, carbon nanoparticles, gold nanoparticles, quantum dots, upconversion nanoparticles, and polymeric micelles. Additional nanoformulations including supramolecular self-assembled structures, proteins, peptides, metal-organic frameworks, and coordination polymers will then be described. Finally, the significant clinical progress made by nanoparticle formulations of platinum(II) agents will be reviewed. We anticipate that such a synthesis of disparate research efforts will not only help to generate new drug development ideas and strategies, but also reflect our optimism that the next generation of platinum cancer drugs is about to arrive.

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“…12−14 While many of the new chemical entities show promising efficacy, the understanding of their biological activities is often incomplete. The very nature of inorganic agents (with variable charge states, geometries, and coordination numbers, all of which can be altered by speciation) adds to the challenge and can result in polypharmacology.…”

Section: Introductionmentioning

confidence: 99%

Bacterial Cytological Profiling Reveals the Mechanism of Action of Anticancer Metal Complexes

et al. 2018

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Target identification and mechanistic studies of cytotoxic agents are challenging processes that are both time-consuming and costly. Here we describe an approach to mechanism of action studies for potential anticancer compounds by utilizing the simple prokaryotic system, E. coli, and we demonstrate its utility with the characterization of a ruthenium polypyridyl complex [Ru(bpy)2dmbpy2+]. Expression of the photoconvertible fluorescent protein Dendra2 facilitated both high throughput studies and single-cell imaging. This allowed for simultaneous ratiometric analysis of inhibition of protein production and phenotypic investigations. The profile of protein production, filament size and population, and nucleoid morphology revealed important differences between inorganic agents that damage DNA vs more selective inhibitors of transcription and translation. Trace metal analysis demonstrated that DNA is the preferred nucleic acid target of the ruthenium complex, but further studies in human cancer cells revealed altered cell signaling pathways compared to the commonly administrated anticancer agent cisplatin. This study demonstrates E. coli can be used to rapidly distinguish between compounds with disparate mechanisms of action and also for more subtle distinctions within in studies in mammalian cells.

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Third row transition metals for the treatment of cancer

Cited by 102 publications

References 47 publications

Electrochemical Deposition of Cisplatin on Pure Magnesium

Electrochemical Deposition of Cisplatin on Pure Magnesium

The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs

Bacterial Cytological Profiling Reveals the Mechanism of Action of Anticancer Metal Complexes

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