A subcellular-specific iridium complex boosting cuproptosis for cancer theranostics
Source abstract
Abstract
Cuproptosis, a copper (Cu)-dependent anticancer mechanism, faces challenges in Cu delivery and tracking. Here, we report the first iridium(III) complex with Cu + ion-chelating properties designed for the tracking and delivery of Cu + ions into the mitochondria of triple-negative breast cancer (TNBC) cells to induce cuproptosis. The probe exhibits a specific luminescence binding affinity to Cu + ions (K d of 7.64 × 10 −2 μM, 1:1 stoichiometry). The Cu + -loaded probe induces oligomerization of the cuproptosis marker DLAT, disrupting the tricarboxylic acid (TCA) cycle, elevating reactive oxygen species (ROS), depleting adenosine triphosphate (ATP) and glutathione (GSH), and impairing the iron-sulfur (Fe-S) cluster protein lipoyl synthase (LIAS), collectively amplifying cuproptosis to kill TNBC cells. In vivo studies confirmed negligible toxicity of the Cu + -loaded probe in mice, highlighting its potential application in preclinical studies. This work provides a strategy for the development of efficient theranostic probes that act by boosting cuproptosis.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Molecular Sensors and Ion Detection · Advanced biosensing and bioanalysis techniques · Nanocluster Synthesis and Applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (34)
Show source-provided references
1. Cuproptosis induced by ROS responsive nanoparticles with elesclomol and copper combined with αPD-L1 for enhanced cancer immunotherapy10.1002/adma.202370152 ↗
2. Metalloallostery and transition metal signaling: bioinorganic copper chemistry beyond active sites10.1002/anie.202213644 ↗
3. Cuproptosis: Harnessing transition metal for cancer therapy10.1021/acsnano.3c07775 ↗
4. Copper induces cell death by targeting lipoylated TCA cycle proteins10.1126/science.abf0529 ↗
5. Copper-induced cell death10.1126/science.abo3959 ↗
6. Photothermally triggered copper payload release for cuproptosis-promoted cancer synergistic therapy
7. CuCo2O4 nanoflowers with multiple enzyme activities for treating bacterium-infected wounds via cuproptosis-like death10.1021/acsnano.4c02825 ↗
8. In situ hydrogel based on Cu–Fe3O4 nanoclusters exploits oxidative stress and the ferroptosis/cuproptosis pathway for chemodynamic therapy10.1016/j.biomaterials.2024.122675 ↗
9. Nanoarchitectonics of in situ antibiotic-releasing acicular nanozymes for targeting and Inducing cuproptosis-like death to eliminate drug-resistant bacteria10.1021/acsnano.4c06565 ↗
10. Intelligent gold nanoparticles for malignant tumor treatment via spontaneous copper manipulation and on-demand photothermal therapy based on copper induced click chemistry10.1016/j.actbio.2023.04.036 ↗
11. Redox homeostasis disruptors based on metal-phenolic network nanoparticles for chemo/chemodynamic synergistic tumor therapy through activating apoptosis and cuproptosis
12. Connecting copper and cancer: from transition metal signalling to metalloplasia10.1038/s41568-021-00417-2 ↗
13. Chemotherapy mediated by biomimetic polymeric nanoparticles potentiates enhanced tumor immunotherapy via amplification of endoplasmic reticulum stress and mitochondrial dysfunction10.1002/adma.202206861 ↗
14. Copper-based nanomaterials for the treatment of bacteria-infected wounds: material classification, strategies and mechanisms10.1016/j.ccr.2024.216205 ↗
15. A stimuli-responsive small-molecule metal-carrying prochelator: A novel prodrug design strategy for metal complexes
16. Synthesis, crystallographic characterization and electrochemical property of a copper(II) complex of the anticancer agent elesclomol10.1016/j.jinorgbio.2013.10.005 ↗
17. Peptide-conjugated long-lived theranostic imaging for targeting GRPr in cancer and immune cells10.1002/anie.202007920 ↗
18. Type-I AIE photosensitizer loaded biomimetic system boosting cuproptosis to inhibit breast cancer metastasis and rechallenge10.1021/acsnano.3c00326 ↗
19. A Phosphine Oxide-Functionalized Cyclam as a Specific Copper (II) Chelator10.1021/acs.inorgchem.3c00329 ↗
20. Rational design, synthesis of fluorescence probes for quantitative detection of amyloid-β in Alzheimer’s disease based on rhodamine-metal complex10.1021/acs.analchem.2c01911 ↗
21. Ligand-tuneable, red-emitting iridium(III) complexes for efficient triplet–triplet annihilation upconversion performance10.1002/chem.201801007 ↗
22. Spectroscopic and theoretical investigation of color tuning in deep-red luminescent iridium(III) complexes10.1021/acs.inorgchem.9b02991 ↗
23. Combining ruthenium(II) complexes with metal–organic frameworks to realize effective two-photon absorption for singlet oxygen generation10.1021/acsami.6b05817 ↗
24. Copper metabolism as a unique vulnerability in cancer10.1016/j.bbamcr.2020.118893 ↗
25. Electroanalytical sensor based on gold-nanoparticle-decorated paper for sensitive detection of copper ions in sweat and serum10.1021/acs.analchem.0c05469 ↗
26. Relationship between serum copper, ceruloplasmin, and non–ceruloplasmin-bound copper in routine clinical practice10.1373/clinchem.2005.052688 ↗
27. Tb-metal organic frameworks-referenced bathocuproine disulfonate enable fluorescence distinguishing Cu+ from Cu2+10.1016/j.snb.2023.134487 ↗
28. An enzyme-engineered nonporous copper (I) coordination polymer nanoplatform for cuproptosis-based synergistic cancer therapy10.1002/adma.202204733 ↗
29. Cu-related agents for cancer therapies10.1016/j.ccr.2023.215156 ↗
30. Self-destructive copper carriers induce pyroptosis and cuproptosis for efficient tumor immunotherapy against dormant and recurrent tumors10.1002/adma.202308241 ↗
31. Focus on cuproptosis: Exploring new mechanisms and therapeutic application prospects of cuproptosis regulation10.1016/j.biopha.2024.117182 ↗
32. Cuproptosis-driven enhancement of thermotherapy by sequentially response Cu2-xSe via copper chemical transition10.1002/adfm.202302054 ↗
33. Design of topology-controlled polyethers toward robust cooperative hydrogen bonding10.1002/adfm.202370198 ↗
34. A modular ionophore platform for liver-directed copper supplementation in cells and animals10.1021/jacs.8b08014 ↗