Cancer is the most serious world's health problems on the global level and various strategies have been developed for cancer therapy. Pillar[5]arene-based supramolecular therapeutic nano-platform (SP/GOx NPs) was constructed successfully via orthogonal dynamic covalent bonds and intermolecular H-bonds with the assistance of glucose oxidase (GOx) and exhibited efficient targeted/synergistic chemo-chemodynamic cancer therapy.The morphology of SP/GOx NPs was characterized by DLS, TEM, SEM and EDS mapping. The cancer therapy efficinecy was investigated both in vivo and in vitro.SP/GOx NPs can load drug molecules (Dox) and modify target molecule (FA-Py) on its surface conveniently. When the resultant FA-Py/SP/GOx/Dox NPs enters blood circulation, FA-Py will target it to cancer cells efficiently, where GOx can catalyst the overexpressed glucose to generate H2O2. Subsequently, the generated H2O2 in cancer cells catalyzed by ferrocene unit to form •OH, which can kill cancer cells. Furthermore, the loaded Dox molecules released under acid microenvironment, which can further achieve chemo-therapy.All the experiments showed that the excellent antitumor performance of FA-Py/SP/GOx/Dox NPs, which provided an new method for pillar[5]arene-based supramolecular polymer for biomedical applications. 

https://jnanobiotechnology.biomedcentral.com/counter/pdf/10.1186/s12951-021-01237-0

GOx-assisted synthesis of pillar[5]arene based supramolecular polymeric nanoparticles for targeted/synergistic chemo-chemodynamic cancer therapy

Twelve new complexes Cu(L1)2-Cu(L12)2 were designed and synthesized to improve their chemotherapeutic properties. They showed considerable antiproliferative activity against T24 cancer cells but lower cytotoxicity to human normal cells HL-7702 and WI-38. A mechanism study indicated that Cu(L4)2 and Cu(L10)2 were reduced to Fenton-like Cu+ by glutathione depletion, and the resulting Cu+ catalyzed the generation of highly toxic hydroxyl radicals from excess H2O2. Simultaneously, Cu(L4)2 and Cu(L10)2 could decrease the catalase activity to restrain H2O2 transfer to H2O for enhanced chemodynamic therapy (CDT). These induced mitochondrial dysfunctions and endoplasmic reticulum stress to induce T24 cell apoptosis. In addition, Cu(L4)2 and Cu(L10)2 inhibited autophagy flux to promote cell apoptosis. Cu(L4)2 and Cu(L10)2 demonstrated strong tumor inhibition ability in the T24 xenograft model. Moreover, Cu(L10)2 showed higher antitumor activity and a better safety profile than the CDT agent Cu1. Cu(L10)2 exhibited excellent pharmacokinetic properties. Collectively, Cu(L4)2 and Cu(L10)2 could be developed as potential CDT candidates for cancer treatment.

Copper(II) Complexes of Halogenated Quinoline Schiff Base Derivatives Enabled Cancer Therapy through Glutathione-Assisted Chemodynamic Therapy and Inhibition of Autophagy Flux.

A palladium(II) complex with the Schiff base 4-chloro-2-(N-ethyliminomethyl)-phenol: Synthesis, structural characterization, and in vitro and in silico biological activity studies.

Copper, a transition metal, serves as an essential co-factor in numerous enzymatic active sites and constitutes a vital trace element in the human body, participating in crucial life-sustaining activities such as energy metabolism, antioxidation, coagulation, neurotransmitter synthesis, iron metabolism, and tetramer deposition. Maintaining the equilibrium of copper ions within biological systems is of paramount importance in the prevention of atherosclerosis and associated cardiovascular diseases. Copper induces cellular demise through diverse mechanisms, encompassing reactive oxygen species responses, apoptosis, necrosis, pyroptosis, and mitochondrial dysfunction. Recent research has identified and dubbed a novel regulatory cell death modality-"cuprotosis"-wherein copper ions bind to acylated proteins in the tricarboxylic acid cycle of mitochondrial respiration, resulting in protein aggregation, subsequent downregulation of iron-sulfur cluster protein expression, induction of proteotoxic stress, and eventual cell death. Scholars have synthesized copper complexes by combining copper ions with various ligands, exploring their significance and applications in cancer therapy. This review comprehensively examines the multiple pathways of copper metabolism, copper-induced regulatory cell death, and the current status of copper complexes in cancer treatment. 

Copper-instigated modulatory cell mortality mechanisms and progress in oncological treatment investigations

Cu-related agents for cancer therapies

A simple and feasible atom-precise biotinylated Cu(I) complex for tumor-targeted chemodynamic therapy

Based on 1,2-dimethoxyphenyl (veratrole, open) and 1,2-methylenedioxyphenyl (pepper ring, close)-derived pyridine–triazole analogues, two groups of copper(II) complexes, namely, Group I(C1–C3) and Group II(C4–C6) were synthesized and fully characterized. All ligands and complexes were tested in vitro by MTT assays on seven tumour cell lines (T24, Hep-G2, Sk-Ov-3, MGC-803, HeLa, A549 and NCI-H460) and one normal liver cell line (HL-7702). Surprisingly, the pepper-ring-derived complexes (C4–C6) showed significantly enhanced cytotoxicity compared with the 1,2-bimethoxyphenyl ring-derived complexes (C1–C3) and the standard anticancer drug cisplatin. Cellular uptake assays indicated that the Cu accumulation was consistent with cytotoxicity. In addition, flow cytometry and western blot analysis showed that the apoptosis of the leading complex C4 may be induced by the Bcl-2 family-mediated proteins through the mitochondrial dysfunction pathway. Furthermore, UV-vis and fluorescence spectroscopy assays revealed that C4 has stronger insertion-binding interactions with CT-DNA than C1 and the fluorescence of C1 and C4 with BSA is mainly quenched by static quenching.

/pdf/two-groups-of-copperii-pyridine-triazole-complexes-with-open-369cp5zton.pdf

Two groups of copperII pyridine–triazole complexes with “open or close” pepper rings and their in vitro antitumor activities

Synthesis, crystal structures and antioxidant activities of water-soluble salicylaldehyde Schiff base complexes

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A simple and feasible atom-precise biotinylated Cu(I) complex for tumor-targeted chemodynamic therapy

Two groups of copperII pyridine–triazole complexes with “open or close” pepper rings and their in vitro antitumor activities

Synthesis, crystal structures and antioxidant activities of water-soluble salicylaldehyde Schiff base complexes