Gallium (III) Complexes in Cancer Chemotherapy

Peng, Xin‐Xin; Gao, Song; Zhang, Junlong

doi:10.1002/ejic.202100953

Cited by 22 publications

(24 citation statements)

References 96 publications

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“…After 24 incubation of 1000 μg/mL of Ga droplets in DMEM at 37 °C, the concentration of Ga ions was measured to be 20 μg/mL (286 μM), compared to 1 μg/mL (3 μM) immediately following sonication. Gallium complexes have previously shown toxic effects to cancerous and noncancerous cell lines at similar concentrations. − This is thought to be due to iron mimicry and in lesser part, altering the pH in aqueous solutions. ,, Therefore, it was hypothesized that leached Ga 3+ ions are likely to contribute to the cytotoxic activity of the Ga droplets. To test this, HaCaT cells were incubated in DMEM containing different concentrations of Ga(NO 3 ) 3 , which readily dissolves to form Ga 3+ (aq) and NO 3 – (aq) in aqueous solution.…”

Section: Resultsmentioning

confidence: 99%

“…63−65 This is thought to be due to iron mimicry and in lesser part, altering the pH in aqueous solutions. 48,64,65 Therefore, it was hypothesized that leached Ga 3+ ions are likely to contribute to the cytotoxic activity of the Ga droplets. To test this, HaCaT cells were incubated in DMEM containing different concentrations of Ga(NO 3 ) 3 , which readily dissolves to form Ga 3+ (aq) and NO 3 − (aq) in aqueous solution.…”

Section: Synthesis and Characterization Of Ga Dropletsmentioning

confidence: 99%

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Assessment of the Cytotoxicity of Nano Gallium Liquid Metal Droplets for Biomedical Applications

Cheeseman

Bryant

Huang

et al. 2022

ACS Appl. Nano Mater.

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Gallium-based liquid metals (LMs) have emerged as novel materials for biomedical applications. Gallium (Ga) is considered significantly less toxic than other LMs, such as mercury. However, Ga droplets have not been thoroughly assessed for their cytotoxicity. Here, we report the concentration-dependent cytotoxic effects of Ga nano- and microdroplets on HaCaT cells, a human keratinocyte cell line. We found that Ga droplets demonstrated substantial cytotoxic effects at 1000 μg/mL after 24 h exposure, while lower concentrations such as 500 μg/mL indicated only a slight reduction in cell viability at longer exposure times. At higher concentrations, it was observed that the cells were unable to form confluent layers and the cytoplasmic membrane became damaged. The formation of a protein corona on the Ga droplets in cell media is also described, which will be an important consideration for future research on Ga droplets for bio-applications. Importantly, this work provides an indication of the concentration at which Ga droplets become damaging to human cells, which will be useful information for a wide range of researchers and regulatory bodies.

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Section: Resultsmentioning

confidence: 99%

Section: Synthesis and Characterization Of Ga Dropletsmentioning

confidence: 99%

Assessment of the Cytotoxicity of Nano Gallium Liquid Metal Droplets for Biomedical Applications

Cheeseman

Bryant

Huang

et al. 2022

ACS Appl. Nano Mater.

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“…9 To further enhance the pharmacological and biological properties of the metal, several gallium-based complexes were synthesized in the last few years. 10 Given the long-term experience of our research group on the study of pyrazolone-based ligands as anticancer and antibacterial agents, 11,12 we investigated the effect of the coordination of these molecules with Ga(III). In fact, the pyrazolone scaffold is a pharmacophore of many chemotherapeutics, 13 this core molecule being associated with a broad spectrum of biological activities, such as antibacterial, analgesic, antioxidant, and (mainly) antitumoral.…”

Section: ■ Introductionmentioning

confidence: 99%

Multitarget-Directed Gallium(III) Tris(acyl-pyrazolonate) Complexes Induce Ferroptosis in Cancer Cells via Dysregulation of Cell Redox Homeostasis and Inhibition of the Mevalonate Pathway

et al. 2023

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A series of Ga(Q n ) 3 coordination compounds have been synthesized, where HQ n is 1-phenyl-3-methyl-4-RC(�O)pyrazolo-5-one. The complexes have been characterized through analytical data, NMR and IR spectroscopy, ESI mass spectrometry, elemental analysis, X-ray crystallography, and density functional theory (DFT) studies. Cytotoxic activity against a panel of human cancer cell lines was determined by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, with interesting results in terms of both cell line selectivity and toxicity values compared with cisplatin. The mechanism of action was explored by spectrophotometric, fluorometric, chromatographic, immunometric, and cytofluorimetric assays, SPR biosensor binding studies, and cell-based experiments. Cell treatment with gallium(III) complexes promoted several cell death triggering signals (accumulation of p27, PCNA, PARP fragments, activation of the caspase cascade, and inhibition of the mevalonate pathway) and induced changes in cell redox homeostasis (decreased levels of GSH/GPX4 and NADP(H), increased reactive oxygen species (ROS) and 4hydroxynonenal (HNE), mitochondrial damage, and increased activity of CPR and CcO), identifying ferroptosis as the mechanism responsible for cancer cell death.

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“…Encouraged by the results of GaM and KP46 in clinical trials, novel Ga(III) complexes with preclinical antitumor activity exploited. 13–15 Researchers are very interested in exploring more gallium(III) complexes with other reasonable substituents of 8-hydroxyquinoline ligands, among which 5-bromo-8-hydroxyquinoline (HBrQ) has been shown to have some anticancer activity in the study, 16 , 17 so HBrQ can be selected as an organic ligand for gallium(III) complex. On the other hand, due to pharmacological inadequacies such limited bioavailability, 18 poor water solubility, 19 drug resistance, and short circulation durations, the fast development of metal-complexed medications poses additional difficulties.…”

Section: Introductionmentioning

confidence: 99%

Gallium Metal−Organic Nanoparticles with Albumin-Stabilized and Loaded Graphene for Enhanced Delivery to HCT116 Cells

Wu¹,

Liao²,

Niu³

et al. 2023

IJN

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Background Gallium (III) metal-organic complexes have been shown to have the ability to inhibit tumor growth, but the poor water solubility of many of the complexes precludes further application. The use of materials with high biocompatibility as drug delivery carriers for metal-organic complexes to enhance the bioavailability of the drug is a feasible approach. Methods Here, we modified the ligands of gallium 8-hydroxyquinolinate complex with good clinical anticancer activity by replacing the 8-hydroxyquinoline ligands with 5-bromo-8-hydroxyquinoline (HBrQ), and the resulting Ga(III) + HBrQ complex had poor water solubility. Two biocompatible materials, bovine serum albumin (BSA) and graphene oxide (GO), were used to synthesize the corresponding Ga(III) + HBrQ complex nanoparticles (NPs) BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs in different ways to enhance the drug delivery of the metal complex. Results Both of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs can maintain stable existence in different solution states. In vitro cytotoxicity test showed that two nanomedicines had excellent anti-proliferation effect on HCT116 cells, which shown higher level of intracellular ROS and apoptosis ratio than that of cisplatin and oxaliplatin. In addition, the superior emissive properties of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs allow their use for in vivo imaging showing highly effective therapy in HCT116 tumor-bearing mouse models. Conclusion The use of biocompatible materials for the preparation of NPs against poorly biocompatible metal-organic complexes to construct drug delivery systems is a promising strategy that can further improve drug delivery and therapeutic efficacy.

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Gallium (III) Complexes in Cancer Chemotherapy

Cited by 22 publications

References 96 publications

Assessment of the Cytotoxicity of Nano Gallium Liquid Metal Droplets for Biomedical Applications

Assessment of the Cytotoxicity of Nano Gallium Liquid Metal Droplets for Biomedical Applications

Multitarget-Directed Gallium(III) Tris(acyl-pyrazolonate) Complexes Induce Ferroptosis in Cancer Cells via Dysregulation of Cell Redox Homeostasis and Inhibition of the Mevalonate Pathway

Gallium Metal−Organic Nanoparticles with Albumin-Stabilized and Loaded Graphene for Enhanced Delivery to HCT116 Cells

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