Ferroptotic cancer therapy has been extensively investigated since the genesis of the ferroptosis concept. However, the therapeutic efficacy of ferroptosis induction in heterogeneous and plastic melanoma has been compromised, because the melanocytic and transitory cell subpopulation is resistant to iron-dependent oxidative stress. Here, we report a phenotype-altering liposomal nanomedicine to enable the ferroptosis-resistant subtypes of melanoma cells vulnerable to lipid peroxidation via senescence induction. The strategy involves the ratiometric coencapsulation of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor (palbociclib) and a ferroptosis inducer (auranofin) within cRGD peptide-modified targeted liposomes. The two drugs showed a synergistic anticancer effect in the model B16F10 melanoma cells, as evidenced by the combination index analysis (<1). The liposomes could efficiently deliver both drugs into B16F10 cells in a targeted manner. Afterward, the liposomes potently induced the intracellular redox imbalance and lipid peroxidation. Palbociclib significantly provoked cell cycle arrest at the G0/G1 phase, which sensitized auranofin-caused ferroptosis through senescence induction. Meanwhile, palbociclib depleted intracellular glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH), further boosting ferroptosis. The proof-of-concept was also demonstrated in the B16F10 tumor-bearing mice model. The current work offers a promising ferroptosis-targeting strategy for effectively treating heterogeneous melanoma by manipulating the cellular plasticity.

Ovarian cancers (OC) often resist current standard chemotherapy because of the cancer heterogeneity and overexpression of an anti-apoptotic protein, myeloid cell leukemia-1 (MCL-1). The heterogeneous OC shows impaired redox homeostasis and relies heavily on glutathione peroxidase 4 to eliminate toxic lipid peroxides. Therefore, integrated apoptosis and ferroptosis therapy is promising for OC management. The current work reports a liposomal nanosystem for apoptotic and ferroptotic OC therapy. Simvastatin (Sim) and vorinostat (Saha) were selected as the pleiotropic model drugs. The successive release of Saha and Sim from liposomes enabled the sequential amplification of MCL-1 by Saha, and then MCL-1 inhibition by Sim. Such a strategy could potently induce apoptosis in a human OC cell line (SKOV3), as indicated by increased intracellular cytochrome c concentration, caspase 3/9 activity, and the extent of apoptosis. Besides, Saha played multiple roles in cell death. It could induce cell cycle arrest at the G(2)/M phase and apoptosis. Saha also inhibited the glutamate-cystine transporter (SLC7A11) and provoked ferroptosis, which was corroborated by the depletion of glutathione, reduced nicotinamide adenine dinucleotide phosphate, and boost of lipid peroxides and malondialdehyde in SKOV3 cells. The current work integrated the "sequential amplification and inhibition of MCL-1 target" concept with combinational apoptosis and ferroptosis OC therapy, which might offer a new approach for managing resistant OC and other malignant diseases.

The dose‐dependent cardiomyopathy of adriamycin (doxorubicin) limits its long‐term clinical use, which is revealed as a consequence of cardiomyocyte ferroptosis. As a ferrous iron (Fe 2 + )‐dependent regulated cell death pathway, ferroptosis is induced by the tailored lipid peroxides in the cell membranes. Herein, iron‐chelating polymer micelles are reported for concurrent doxorubicin delivery and cardiotoxicity reduction. The amphiphilic polymer consists of methoxy poly (ethylene glycol)‐ co ‐poly (glutamic acid) copolymer as the backbone and deferiprone analog as the side chain. The chiral polymer adopted the α‐helix conformation to enable prolonged retention in the cell membranes, resulting in efficient iron chelation, ferroptosis inhibition, and cardiotoxicity reduction. The co‐encapsulation of doxorubicin and coenzyme Q 10 (CoQ 10 ) in micelles further alleviates the cardiotoxicity because the reduced CoQ 10 can act as a radical trapping agent to constrain lipid peroxidation and cardiomyocyte ferroptosis. The reduction of cardiotoxicity is accompanied by enhanced anticancer efficacy in an in vivo murine breast cancer model. The chiral iron‐chelating polymer micelles can be a promising platform for enhanced doxorubicin delivery and reduced cardiac adverse effects.

Melanoma is a highly lethal form of skin cancer. Although targeted drugs and immunotherapy have definite survival benefits for certain patients, they also encounter systemic toxicity and drug resistance concerns. With nanotechnology developments and the in-depth antigen and receptor study on melanoma cells, nanoparticles functionalized with different ligands (such as antibodies, aptamers, peptides, folate, hyaluronic acid, and transferrin) are utilized in targeted drug delivery systems. In addition, combining biomimetics and nanotech-nology provides a developmental platform for constructing cell membrane-camouflaged nanoparticles. Nano -particles coated with melanoma or immune cell membranes have been scrutinized for melanoma therapy use. These targeting strategies encourage drug accumulation at the tumor site, enhance antitumor efficacy, and reduce systemic toxicity. Exploring new melanoma targets will promote novel target molecule development and high-loading multifunctional targeting nanoparticle production, further improving therapeutic effects. This re-view highlights recent advances in targeted nanoparticle drug delivery systems for melanoma therapy.

Solvothermal reactions of mixed ligands H(3)BTC and macrocyclic oxamide complexes (ML, M = Cu, Ni) with M(ClO(4))(2)·6H(2)O (M = Co, Zn, Ni and Cd) afford six new complexes, including [M'(4)(BTC)(2)(ML)(2)(OH)(2)(H(2)O)(2)]·2H(2)O (M' = Co, M = Ni, for (1); M' = Zn, M = Ni, for (2); M' = Zn, M = Cu, for (3)), [Ni(3)(BTC)(2)(NiL)(2)(H(2)O)(6)]·2CH(3)OH·2H(2)O (4), [Cd(4)(BTC)(2)(HBTC)(NiL)(4)(H(2)O)]·3H(2)O (5) and [Cd(HBTC)(CuL)]·H(2)O (6) (ML, H(2)L = 2, 3-dioxo-5, 6, 14, 15-dibenzo-1,4,8,12-tetraazacyclo-pentadeca-7,13-dien; H(3)BTC = 1,3,5-benzenetricarboxylic acid). Complexes 1-3 consist of a 2D layer framework formed by the linkage of M(II)(M = Ni, Cu) and M'(4) (M' = Co, Zn) cluster via the oxamide and BTC(3-) bridges and display a (3,6)-connected network with a (4(3))(2)(4(6).6(6).8(3)) topology. The structure of 4 consists of pentanuclear [Ni(II)(5)] units and arranges in a 1D cluster chain. Complex 5 exhibits a 2D layered structure characterized by 3,4,3-connected (4.6(2))(3)(4.6(3).8(2))(4(2).6(3).8)(4(2).6) topology. Complex 6 possesses a 3D network with sra topology. The magnetic properties of complexes 1 and 4 were investigated.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Three novel complexes, namely [Zn(CuL)(pzdc)]2 center dot 5H2O (1), [Zn(NiL)(pzdc)]2 center dot 5H2O (2), and [Gd2(pzdc)2(NiL)6](ClO4)2 center dot 6H2O (3) (CuL and NiL, H2L = 2, 3-dioxo-5, 6, 14, 15-dibenzo-1, 4, 8, 12-tetraazacyclo-pentadeca-7, 13-dien and H2pzdc = pyrazine-2, 3-dicarboxylic acid) were synthesized and structurally determined. Complexes 1 and 2 are tetranuclear [ZnII2MII2] (M = Ni (1), Cu (2), respectively) molecules including both oxamide and pzdc2 bridges. The structure of compound 3 consists of pyrazine-2, 3-dicarboxylate and oxamido-bridged, and is arranged in different butterfly-like octanuclear molecules. The magnetic susceptibility data of 3 were analyzed.

The complex (Zn4.5(SSA)3(CuL)3(H2O)6)n was synthesized and structurally determined, where SSA is fully deprotonated 5-sulfosalicylic acid(CuL, H2L=2,3-dioxo-5,6,14,15-dibenzo-1,4,8,12-tetraazacyclo-pentadeca- 7,13-dien). The title complex crystallized in the triclinic system with space group P1ത , a=1.19788(17) nm, b=1.4253(2) nm, c=2.2890(4) nm, α=90.211(2)°, β=93.076(2)°, γ=90.600(2)°. The complex displayed a 1D ladderlike chain. All these 1D chains were further interlinked via hydrogen bonds, resulting in a 2D architecture. The luminescent property of the compound was also discussed. Keywords Heteronuclear complex; Macrocyclic oxamide; Luminescence Article ID 1005-9040(2010)-04-501-04

The complex [Zn-4.5(SSA)(3)(CuL)(3)(H2O)(6)](n) was synthesized and structurally determined, where SSA is fully deprotonated 5-sulfosalicylic acid(CuL, H2L=2,3-dioxo-5,6,14,15-dibenzo-1,4,8,12-tetraazacyclo-pentadeca-7,13-dien). The title complex crystallized in the triclinic system with space group P (1) over bar, a=1.19788(17) nm, b=1.4253(2) nm, c=2.2890(4) nm, alpha=90.211(2)degrees, beta=93.076(2)degrees, gamma=90.600(2)degrees. The complex displayed a 1D ladderlike chain. All these ID chains were further interlinked via hydrogen bonds, resulting in a 2D architecture. The luminescent property of the compound was also discussed.

Two novel heteronuclear complexes [Cd3(SSAL)2(CuL)2(H2O)4]n (1) and [Cd2(HSSAL)2(NiL)4]·4H2O (2) were synthesized and structurally determined, where SSAL is the fully deprotonated 5-sulfosalicylic ion (CuL and NiL, H2L = 2,3-dioxo-5,6,14,15-dibenzo-1,4,8,12-tetraazacyclopentadeca-7,13-diene). Compound 1 displays a 1D ladder-like chain and all these chains are further interlinked through hydrogen bonds resulting in a 2D architecture. The structure of 2 consists of 5-sulfosalicylates and an oxamido-bridge and is arranged in butterfly-like hexanuclear molecules. The luminescent properties of compounds 1 and 2 are also discussed.

Two heterometallic trinuclear complexes of macrocyclic oxamide [Co(NiL1)(2)L-2(H2O)].3H(2)O (1) and [Mn(NiL1)(2)L-2(H2O)]center dot 0.5CH(3)OH center dot 1.5H(2)O (2) (H2L1 = 2,3-dioxo-5,6,14,15-dibenzo-1,4,8,12-tetraazacyclopentadeca- 7,13-diene, H2L2 = 5-sulfosalicylic acid) were synthesized and structurally characterized by elemental analysis, IR spectroscopy, and X-ray diffraction. Single-crystal X-ray analyses reveal that both the complexes contain discrete neutral trinuclear [(NiL1)(2)ML2(H2O)] (for 1 and 2, M = Co, Mn, respectively) moieties. The structures of 1 and 2 have oxamido-bridged trinuclear [(MNi2II)-Ni-II] units and consist of one-dimensional chains formed by strong intermolecular hydrogen bonds. Furthermore, the magnetic properties of complex 1 were investigated and discussed in detail.

The complex incorporating macrocyclic oxamide of the formula [(CuL)2Cd(NCS)2] (H2L = 2,3-dioxo-5,6,14,15-dibenzo-1,4,8,12-tetraazacyclo-pentadeca-7,13-diene) has been synthesized and structurally characterized. The crystals crystallize in the monoclinic system, space group C2/c, a = 13.865(3), b = 14.390(3), c = 38.252(8) Å, β = 92.45(3)°, Z = 8. The crystal structure unit is a trianuclear complex in which the Cd2+ and Cu2+ ions are bridged by the macrocyclic oxamide groups. The [(CuL)2Cd(NCS)2] units are alternately bridged by C-H···O to C-H···S hydrogen bond to form a 2D framework. The luminescent property of the compound is also discussed.

The organic-inorganic hybrid complex with formula [(CuL)(2)Cu-3(mu-1,1-N-3)(4)(ClO4)(2)], complex 1, {CuL, [5,6:14,15-dibenzo-1,4,8,12-tetraazacyclopentadeca-7,13-diene-2,3-dione(2-)]copper(II)}, has been synthesized and structurally determined. The crystals of complex 1 crystallize in the triclinic system with space group P!, a=0.92983(12) nm, b=1.09644(14) nm, c=1.27396(16) nm, alpha=70.782(2)degrees, beta=86.266(2)degrees, gamma=78.284(2)degrees. In this complex, the five copper ions are bridged by macrocyclic oxamide groups and azido. Furthermore, C-H center dot center dot center dot O hydrogen bond interactions link the pentanuclear fragments to form a 2D supramolecular architecture.

Hydrothermal reactions of mixed ligands 5-sulfosalicylic acid (H(3)SSAL) and macrocyclic oxamide complex (CuL) with M(ClO(4))(2)·6H(2)O (M = Mn, Gd and Cu) afford three new complexes, including [Mn(II)(2)Mn(III)(SSAL)(2)(CuL)(2)(OH)(H(2)O)(3)]n (1), {[Gd(2)(HSSAL)(2)(CuL)(4)(C(2)O(4))(H(2)O)(2)]·2H(2)O}(n) (2) and [Cu(2)(HSSAL)(2)(CuL)(4)]·2H(2)O (3) (CuL, H(2)L = 2,3-dioxo-5,6,14,15-dibenzo-1,4,8,12-tetraazacyclo-pentadeca-7,13-diene). Complex 1 has very interesting mixed-valence manganese-copper Cu(II)Mn(II)Mn(III)Mn(II)Cu(II) units and consists of a 1D ladderlike chain formed by the linkage of copper(ii) and Mn(3) clusters via the oxamide and SSAL(3-) bridges. The structure of 2 consists of hexanuclear Cu(II)(4)Gd(III)(2) molecules and is arranged in a 1D ladderlike chain formed by the linkage of copper(ii) and gadolinium(iii) via the oxamide, oxalate and HSSAL(2-) bridges. Complex 3 is a hexanuclear Cu(II)(6) molecule including both oxamide and HSSAL(2-) bridges. The results of magnetic determination show pronounced antiferromagnetic interactions in 1 and 3, and ferromagnetic interactions in 2.

Macrocyclic lanthanon-transitional supermolecular complex [Tb(NiL)3(CH3OH)3](ClO4)3·5CH3OH(1) has been synthesized and structurally determined by X-ray diffraction,IR spectrum and electronic spectrum.1 crystallizes in the triclinic system with P-1 group,a = 1.508 1(3) nm,b=1.513 2(3) nm,c=1.744 6(3) nm,α=82.512(11)o,β=70.095(6)o,γ=84.185(10)o,Z=2.