Revisiting metallodrugs for the treatment of skin cancers

Manzano, Carlos Marrote; Nakahata, Douglas Hideki; Paiva, Raphael Enoque Ferraz de

doi:10.1016/j.ccr.2022.214506

Cited by 13 publications

(5 citation statements)

References 385 publications

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“…[1] Especially for the treatment of skin cancers, the development of such metallodrugs was reviewed very recently. [2] Cyclometalated iridium(III) complexes belong to compounds of potential candidates because they play a crucial role in studies of cancer therapy due to their high cytotoxic activities. [3] Thus, in the last years we investigated the biological activities of many derivatives bearing modified phenanthrolines and related bipyridines as the ancillary ligands.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization and Cytotoxic Activities of Half‐sandwich Pentamethylcyclopentadienyl Iridium(III) Complexes Containing 4,4'‐substituted 2,2'‐Bipyridine Ligands

Graf

Ochs

Metzler‐Nolte

et al. 2023

Zeitschrift anorg allge chemie

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Dedicated to Professor Wolfgang Weigand on the occasion of his 65 th birthdayThe synthesis and characterization of six new organometallic half-sandwich iridium(III) compounds containing modified 4,4'substituted 2,2'-bipyridines as the bidentate co-ligands were described. Thus the compounds [Ir(η 5 -C 5 Me 5 )(N^N)Cl]PF 6 [N^N: 4,4'-bpy-Ph, 1; 4,4'-bpy-Me, 2; 4,4'-bpy-nonyl, 3; 4,4'-bpy-CH 2 OH, 4; 4,4'-bpy-Cl, 5; 4,4'-bpy-NH 2 , 6 were obtained by bridgesplitting reactions from the precursor [{Ir(η 5 -C 5 Me 5 )(μ-Cl)Cl} 2 ] with the corresponding bidentate bipyridines. The X-ray singlecrystal structures of compounds 1, 2, 4 and 6 in the solid state were determined. To evaluate the cytotoxic properties of all six compounds, colorimetric assays (MTT assay) against two cancer cell lines, MCF-7 and HT-29, were performed. Most promising results were achieved for compounds 1 and 3 with nonpolar phenyl or nonyl group attached to the bipyridine ligand, while the substitution with less lipophilic groups led to the inactivation of the compound. The most remarkable biological activity showed compound 3 with an IC 50 value in the low macromolecular range and > 40-fold enhanced toxicity compared to cisplatin against both cell lines.

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Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization and Cytotoxic Activities of Half‐sandwich Pentamethylcyclopentadienyl Iridium(III) Complexes Containing 4,4'‐substituted 2,2'‐Bipyridine Ligands

Graf

Ochs

Metzler‐Nolte

et al. 2023

Zeitschrift anorg allge chemie

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“…Photodynamic therapy (PDT) is a promising approach for cancer treatment, wherein the activation of photosensitizers (PSs) by light irradiation leads to the generation of reactive oxygen species (ROS). This process ultimately induces the noninvasive eradication of tumor cells. , The functionality of PDT is, to a specific extent, dependent on the presence of oxygen. , The efficacy of PDT is significantly diminished in tumors, especially in large solid tumors, due to the presence of a hypoxic environment. , The integration of PDT with various other innovative therapeutic approaches, including photothermal therapy (PTT), photoacoustic therapy (PAT), photochemotherapy (PCT), and immunogenic cell death (ICD), has the potential to synergistically enhance treatment effectiveness and minimize the required dosage of therapeutic agents. − Taking a step back to assert, for PDT alone, the mechanisms underlying the construction of highly active molecules or materials through structural regulation are considered to be largely unidentified. , …”

Section: Introductionmentioning

confidence: 99%

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy

Li,

Zeng,

Yang

et al. 2023

Inorg. Chem.

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Cyclometalated iridium(III) complexes are of significant importance in the field of antitumor photodynamic therapy (PDT), whether they exist as single molecules or are incorporated into nanomaterials. Nevertheless, a comprehensive examination of the relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors of two-photon excited PDT can be anticipated to be further multiplied, particularly in relation to intricate nonlinear optical properties. At present, a comprehensive body of research on this topic is lacking, and few discernible patterns have been identified. In this study, through systematic structure regulation, the nitro-substituted styryl group and 1-phenylisoquinoline ligand containing YQ2 was found to be the most potent infrared two-photon excitable photosensitizer in a 4 × 3 combination library of cyclometalated Ir(III) complexes. YQ2 could enter cells via an energy-dependent and caveolae-mediated pathway, bind specifically to mitochondria, produce 1O2 in response to 808 nm LPL irradiation, activate caspases, and induce apoptosis. In vitro, YQ2 displayed a remarkable phototherapy index for both malignant melanoma (>885) and non-small-cell lung cancer (>1234) based on these functions and was minimally deleterious to human normal liver and kidney cells. In in vivo antitumor phototherapy, YQ2 inhibited tumor growth by an impressive 85% and could be eliminated from the bodies of mice with a half-life as short as 43 h. This study has the potential to contribute significantly to the development of phototherapeutic drugs that are extremely effective in treating large, profoundly located solid tumors as well as the understanding of the structure–activity relationship of Ir(III)-based PSs in PDT.

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“…Photodynamic therapy (PDT) is an effective treatment for various diseases due to its unique advantages of noninvasiveness, spatiotemporal selectivity, and simple operation. , Extensive investigations have approved PDT as a clinical therapy for nonmelanoma skin cancer. , A typical PDT process employs light irradiation of photosensitizers (PSs) to convert in situ oxygen molecules to reactive oxygen species (ROS) to induce cancer cell apoptosis and necrosis . Hence, sufficient oxygen participation is critical to this process.…”

mentioning

confidence: 99%

“…Therefore, it is imperative to develop strategies to ameliorate tumor hypoxia. The unique tumor microenvironment (TME) with the overexpression of H 2 O 2 (100 μM–1 mM, usually at a 5 nmol per 10 5 cells h –1 generation rate) provides some opportunities to address the issue of hypoxic TME. − To date, various smart nanoplatforms have been developed to catalyze H 2 O 2 decomposition to O 2 to ameliorate the hypoxic TME. One kind of nanoplatform is constructed by loading enzymes, such as catalase, into hollow mesoporous nanoparticles, including silicon oxide, Cu 2 MoS 4 , and others. − Although effective O 2 generation was achieved, the encapsulation of enzyme proposed a high requirement that the size of the enzyme matches the pore size of the nanoparticles.…”

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confidence: 99%

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Hierarchical MOF@AuNP/Hairpin Nanotheranostic for Enhanced Photodynamic Therapy via O₂ Self-Supply and Cancer-Related MicroRNA Imaging In Vivo

Yang,

Tian,

Qiu

et al. 2023

Anal. Chem.

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Developing a nanotheranostic with a high sensing performance and efficient therapy was significant in cancer diagnosis and treatment. Herein, a Au nanoparticle and hairpin-loaded photosensitive metal−organic framework (PMOF@AuNP/ hairpin) nanotheranostic was constructed by growing AuNPs on PMOF in situ and then attaching hairpins. On the one hand, the PMOF@AuNP/hairpin nanotheranostic could effectively transfer O 2 into ROS, facilitating efficient PDT. Additionally, the nanotheranostic possessed catalase-like activity, which could effectively catalyze H 2 O 2 to generate O 2 , thus achieving O 2 -evolving PDT and significantly enhancing the antitumor effect of PDT in vivo. On the other hand, the nanotheranostic showed a high loading efficiency of hairpins and achieved the sensitive and selective detection of miR-21 both in living cells and in vivo. Moreover, the nanotheranostic could dynamically monitor the miR-21 level. Due to the excellent imaging performance, the nanotheranostic could recognize cancer cells and might provide important information on cancer progression for PDT. The developed PMOF@AuNP/ hairpin nanotheranostic provided a useful tool for tumor diagnosis and antitumor therapy.

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Revisiting metallodrugs for the treatment of skin cancers

Cited by 13 publications

References 385 publications

Synthesis, Characterization and Cytotoxic Activities of Half‐sandwich Pentamethylcyclopentadienyl Iridium(III) Complexes Containing 4,4'‐substituted 2,2'‐Bipyridine Ligands

Synthesis, Characterization and Cytotoxic Activities of Half‐sandwich Pentamethylcyclopentadienyl Iridium(III) Complexes Containing 4,4'‐substituted 2,2'‐Bipyridine Ligands

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy

Hierarchical MOF@AuNP/Hairpin Nanotheranostic for Enhanced Photodynamic Therapy via O₂ Self-Supply and Cancer-Related MicroRNA Imaging In Vivo

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Revisiting metallodrugs for the treatment of skin cancers

Cited by 13 publications

References 385 publications

Synthesis, Characterization and Cytotoxic Activities of Half‐sandwich Pentamethylcyclopentadienyl Iridium(III) Complexes Containing 4,4'‐substituted 2,2'‐Bipyridine Ligands

Synthesis, Characterization and Cytotoxic Activities of Half‐sandwich Pentamethylcyclopentadienyl Iridium(III) Complexes Containing 4,4'‐substituted 2,2'‐Bipyridine Ligands

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy

Hierarchical MOF@AuNP/Hairpin Nanotheranostic for Enhanced Photodynamic Therapy via O2 Self-Supply and Cancer-Related MicroRNA Imaging In Vivo

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Hierarchical MOF@AuNP/Hairpin Nanotheranostic for Enhanced Photodynamic Therapy via O₂ Self-Supply and Cancer-Related MicroRNA Imaging In Vivo