Recent advances in endoplasmic reticulum targeting metal complexes

Huang, Can; Li, Tingxuan; Liang, Jiayu; Huang, Huaiyi; Zhang, Pingyu; Banerjee, Samya

doi:10.1016/j.ccr.2020.213178

Cited by 54 publications

(44 citation statements)

References 76 publications

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“…With this in mind, we developed a series of copper(II) complexes with a Schiff base ligand, L 1 (a proven ROS mediator once coordinated to copper, see Fig-ure S1 in the Supporting Information for chemical structure) [15,16c,17] and various lipophilic polypyridyl ligands (known to facilitate localisation in the lipid dense ER). [18] The copper(II) complexes, 1-4 used in this study are shown in Figure 1. The complexes, 1-4 were prepared by reacting equimolar amounts of the appropriate polypyridyl ligand with copper(II) nitrate hydrate in methanol, followed by the addition of the Schiff base ligand, L 1 (synthesised according to reported protocols) [16c,19] and excess sodium hexafluorophosphate.…”

Section: Resultsmentioning

confidence: 99%

Immunogenic Cell Death of Breast Cancer Stem Cells Induced by an Endoplasmic Reticulum‐Targeting Copper(II) Complex

et al. 2020

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Immunogenic cell death (ICD) offers a method of stimulating the immune system to attack and remove cancer cells. We report a copper(II) complex containing a Schiff base ligand and a polypyridyl ligand, 4, capable of inducing ICD in breast cancer stem cells (CSCs). Complex 4 kills both bulk breast cancer cells and breast CSCs at sub-micromolar concentrations. Notably, 4 exhibits greater potency (one order of magnitude) towards breast CSCs than salinomycin (an established breast CSC-potent agent) and cisplatin (a clinically approved anticancer drug). Epithelial spheroid studies show that 4 is able to selectively inhibit breast CSC-enriched HMLER-shEcad spheroid formation and viability over non-tumorigenic breast MCF10 A spheroids. Mechanistic studies show that 4 operates as a Type II ICD inducer. Specifically, 4 readily enters the endoplasmic reticulum (ER) of breast CSCs, elevates intracellular reactive oxygen species (ROS) levels, induces ER stress, evokes damageassociated molecular patterns (DAMPs), and promotes breast CSC phagocytosis by macrophages. As far as we are aware, 4 is the first metal complex to induce ICD in breast CSCs and promote their engulfment by immune cells.

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Section: Resultsmentioning

confidence: 99%

Immunogenic Cell Death of Breast Cancer Stem Cells Induced by an Endoplasmic Reticulum‐Targeting Copper(II) Complex

et al. 2020

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“…Cancer is now the leading cause of mortality worldwide, and deaths due to it is expected to rise by ca . 70 % within 2030 [1,2] . Since the discovery of cis‐platin as the anticancer drug and its subsequent FDA approval in early 1960’s, platinum‐based metal complexes such as cis‐platin, oxaliplatin and carboplatin are widely used metal‐based clinical cancer drugs till today [1–4] .…”

Section: Introductionmentioning

confidence: 99%

“…70 % within 2030 [1,2] . Since the discovery of cis‐platin as the anticancer drug and its subsequent FDA approval in early 1960’s, platinum‐based metal complexes such as cis‐platin, oxaliplatin and carboplatin are widely used metal‐based clinical cancer drugs till today [1–4] . But side effects and acquired drug resistance are now limiting the scope of platins against various cancers [1–4] .…”

Section: Introductionmentioning

confidence: 99%

“…Since the discovery of cis‐platin as the anticancer drug and its subsequent FDA approval in early 1960’s, platinum‐based metal complexes such as cis‐platin, oxaliplatin and carboplatin are widely used metal‐based clinical cancer drugs till today [1–4] . But side effects and acquired drug resistance are now limiting the scope of platins against various cancers [1–4] . To fight against the impact of cancer to human health, novel cancer drugs with new mechanism of drug action(s) are of urgent priority to broaden the scope of cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

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Metal‐Based Catalytic Drug Development for Next‐Generation Cancer Therapy

Fan

Huang

et al. 2021

ChemMedChem

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Considering the high increase in mortality caused by cancer in recent years, cancer drugs with novel mechanisms of anticancer action are urgently needed to overcome the drawbacks of platinum‐based chemotherapeutics. Recently, in the area of metal‐based cancer drug development research, the concept of catalytic cancer drugs has been introduced with organometallic RuII, OsII, RhIII and IrIII complexes. These complexes are reported as catalysts for many important biological transformations in cancer cells such as nicotinamide adenine dinucleotide (NAD(P)H) oxidation to NAD+, reduction of NAD+ to NADH, and reduction of pyruvate to lactate. These unnatural intracellular transformations with catalytic and nontoxic doses of metal complexes are known to severely perturb several important biochemical pathways and could be the antecedent of next‐generation catalytic cancer drug development. In this concept, we delineate the prospects of such recently reported organometallic RuII, OsII, RhIII and IrIII complexes as future catalytic cancer drugs. This new approach has the potential to deliver new cancer drug candidates.

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“…However, due to its drug resistance and high toxicity, novel metallic drugs are urgently needed. Recently, metal-based photosensitizers were widely applied for photodynamic therapy (PDT), owing to their high photostability and 1 O 2 generation [5][6][7][8][9][10][11][12][13] . However, one of the bottlenecks of PDT is the low tissue penetration depth of light.…”

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confidence: 99%

A highly potent ruthenium(II)-sonosensitizer and sonocatalyst for in vivo sonotherapy

et al. 2021

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As a basic structure of most polypyridinal metal complexes, [Ru(bpy)3]2+, has the advantages of simple structure, facile synthesis and high yield, which has great potential for scientific research and application. However, sonodynamic therapy (SDT) performance of [Ru(bpy)3]2+ has not been investigated so far. SDT can overcome the tissue-penetration and phototoxicity problems compared to photodynamic therapy. Here, we report that [Ru(bpy)3]2+ is a highly potent sonosensitizer and sonocatalyst for sonotherapy in vitro and in vivo. [Ru(bpy)3]2+ can produce singlet oxygen (1O2) and sono-oxidize endogenous 1,4-dihydronicotinamide adenine dinucleotide (NADH) under ultrasound (US) stimulation in cancer cells. Furthermore, [Ru(bpy)3]2+ enables effective destruction of mice tumors, and the therapeutic effect can reach deep tissues over 10 cm under US irradiation. This work paves a way for polypyridinal metal complexes to be applied to the noninvasive precise sonotherapy of cancer.

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Recent advances in endoplasmic reticulum targeting metal complexes

Cited by 54 publications

References 76 publications

Immunogenic Cell Death of Breast Cancer Stem Cells Induced by an Endoplasmic Reticulum‐Targeting Copper(II) Complex

Immunogenic Cell Death of Breast Cancer Stem Cells Induced by an Endoplasmic Reticulum‐Targeting Copper(II) Complex

Metal‐Based Catalytic Drug Development for Next‐Generation Cancer Therapy

A highly potent ruthenium(II)-sonosensitizer and sonocatalyst for in vivo sonotherapy

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