Xicheng Liu

Fluorinated carbon fiber as a novel nanocarrier for cancer chemo-photothermal therapy

Although biomedical applications of carbon materials such as fullerenes, carbon nanotubes and graphene have been intensively studied in recent years owing to their unique chemical and physical properties, fluorinated carbon fiber (FC) has been rarely explored in biomedicine, mostly because of its large-size, needle-like structure and strong hydrophobicity. In this study, for the first time we developed a novel FC-based nano-carrier with good biocompatibility, high drug-loading capacity and enhanced photo-thermal performance. A simple and feasible strategy is first employed to transform commercial FC into nano-sized ones with good solubility in both water and culture medium. The changes in surface wettability then facilitated us to load doxorubicin (DOX) onto the FC viaπ-π stacking interactions. Successful regulation of structure and composition also endows FC with an enhanced photothermal response in the near-infrared (NIR) region. Moreover, cell experiments indicate that the constructed nanocarrier can be easily transferred into cells by endocytosis, showing low toxicity and exhibiting excellent cancer therapy effects resulting from a good combination of chemotherapy and photothermal therapy. Considering the low cost, high synthesis efficiency and outstanding properties of FC, the newly developed nanocarrier may find widespread applications in biomedicine and other related fields.

Mitochondria-targeted half-sandwich rutheniumII diimine complexes: anticancer and antimetastasis via ROS-mediated signalling

Herein we present half-sandwich RuII diimine complexes that combine anticancer and antimetastasis activity into one molecule. Two half-sandwich RuII diimine complexes [(η6-p-cymene)Ru(N^N)Cl]PF6 have been synthesized and characterized. RuII complexes show antiproliferative activity against a wide range of cancer cell lines in vitro. In addition, they exhibit no cross-resistance with cisplatin. The complexes target mitochondria, damage mitochondrial integrity, and induce mitochondrial membrane permeabilization. Further studies show that the complexes can induce activation of caspase 3/PARP. Interestingly, the complexes finally lead to apoptosis and impede cell migration in cancer cells via ROS-mediated signalling.

Triphenylamine-Appended Half-Sandwich Iridium(III) Complexes and Their Biological Applications

Organometallic half-sandwich IrIII complexes of the type [(η5 -Cpx )Ir(N^N)Cl]PF6 (Cpx : Cp* or its phenyl Cpxph or biphenyl Cpxbiph derivatives; N^N: triphenylamine (TPA)-substituted bipyridyl ligand groups) were synthesized and characterized. The complexes showed excellent bovine serum albumin (BSA) and DNA binding properties and were able to oxidize NADH to NAD+ (NAD=nicotinamide adenine dinucleotide) efficiently. The complexes induced apoptosis effectively and led to the emergence of reactive oxygen species (ROS) in cells. All complexes showed potent cytotoxicity with IC50 values ranging from 1.5 to 7.1u2005μm toward A549 human lung cancer cells after 24u2005hours of drug exposure, which is up to 14u2005times more potent than cisplatin under the same conditions.

Imine-N-Heterocyclic Carbenes as Versatile Ligands in Ruthenium(II) p-Cymene Anticancer Complexes: A Structure-Activity Relationship Study

A family of novel imine-N-heterocyclic carbene ruthenium(II) complexes of the general formula [(η6 -p-cymene)Ru(C^N)Cl]PF6 - (where C^N is an imine-N-heterocyclic carbene chelating ligand with varying substituents) have been prepared and characterized. In this imine-N-heterocyclic carbene chelating ligand framework, there are three potential sites that can be modified, which distinguishes this class of ligand and provides a body of flexibilities and opportunities to tune the cytotoxicity of these ruthenium(II) complexes. The influence of substituent effects of three tunable domains on the anticancer activity and catalytic ability in converting coenzyme NADH to NAD+ is investigated. This family of complexes displays an exceedingly distinct anticancer activity against A549 cancer cells, despite their close structural similarity. Complexu20059 shows the highest anticancer activity in this series against A549 cancer cells (IC50 =14.36u2005μm), with an approximately 1.5-fold better activity than the clinical platinum drug cisplatin (IC50 =21.30u2005μm) in A549 cancer cells. Mechanistic studies reveal that complexu20059 mediates cell death mainly through cell stress, including cell cycle arrest, inducing apoptosis, increasing intracellular reactive oxygen species (ROS) levels, and depolarization of the mitochondrial membrane potential (MMP). Furthermore, lysosomal damage is also detected by confocal microscopy.

Novel iridium(III) iminopyridine complexes: synthetic, catalytic, and in vitro anticancer activity studies

Organometallic half-sandwich IrIII complexes of the type [(η5-Cpx)Ir(N^N)Cl]PF61–6, where Cpxu2009=u2009C5Me5 (Cp*), C5Me4C6H5 (Cpxph), C5Me4C6H4C6H5 (Cpxbiph), N^N is imionopyridine chelating ligand, were prepared and characterized. The X-ray crystal structure of complex 1 has been determined. Four compounds displayed higher anticancer potency than clinically used anticancer drug cisplatin against A549 cancer cells, especially complex 3 which is 8 times more active than cisplatin. No hydrolysis was observed by NMR and UV–Vis for complexes 3 and 6; however, these complexes show big differences in nucleobase binding, mainly decided by the imionopyridine chelating ligand. Complex 3 is stable in the presence of glutathione, but 6 reacted rapidly with glutathione. The octanol/water partition coefficients (log P) of 3 and 6 have been determined. In addition, these complexes display effective catalytic activity in converting coenzyme NADH to NAD+ by accepting hydride to form an Ir hydride adduct. The mechanism of actions of these complexes involves apoptosis induction, cell cycles arrest, and significant increase of reactive oxygen species levels in A549 cancer cells.

Half-sandwich IridiumIII N-heterocyclic carbene antitumor complexes and biological applications

Series of half-sandwich IrIIIN-heterocyclic carbene (NHC) antitumor complexes [(η5-Cp*)Ir(C^C)Cl] have been synthesized and characterized (Cp* is pentamethyl cyclopentadienyl, and C^C are four NHC chelating ligands containing phenyl rings at different positions). IrIII complexes showed potent antitumor activity with IC50 values ranged from 3.9 to 11.8u202fμM against A549 cells by the MTT assay. Complexes can catalyze the conversion of the coenzyme NADH to NAD+ and induce the production of reactive oxygen species (ROS), and bonding to BSA by static quenching mode. Complexes can arrest the cell cycle in G1 or S phase and reduce the mitochondrial membrane potential. Confocal microscopy test show complexes could target the lysosome and mitochondria in cells with the Pearsons colocalization coefficient of 0.82 and 0.21 after 12u202fh, respectively, and followed by an energy-dependent cellular uptake mechanism.

[(η5-pentamethylcyclopentadienyl)(3-fluoro-N-methylbenzylamine-к1,N)dichlorido]iridium(III)

A half-sandwich iridium(III) complex containing 3-fluoro-N-methylbenzylamine ligands has been obtained by reaction of one equivalent of [(η5-Cp*)IrCl2]2 (Cp* = pentamethylcyclopentadienyl) with two equivalent of 3-fluoro-N-methylbenzylamine in very good yield. The structure of this complex was confirmed by X-ray crystallography, 1H-NMR, 13C-NMR spectroscopy, and elemental analysis.

Half-sandwich Iridium(III) Benzimidazole-Appended Imidazolium-Based N-heterocyclic Carbene Complexes and Antitumor Application

A series of half-sandwich iridium(III) benzimidazole-appended imidazolium-based N-heterocyclic carbene (NHC) antitumor complexes [(η5 -Cpx )Ir(C^N)Cl]Cl, where Cpx is pentamethylcyclopentadienyl (Cp*) or its biphenyl derivative (Cpxbiph ) and C^N is a NHC chelating ligand, were successfully synthesized and characterized. The IrIII complexes showed potential antitumor activity against A549 cells, at most three times more potent than cis-platin under the same conditions. Complexes could bind to BSA by a static quenching mode, catalyzing the change of NADH to NAD+ and inducing the production of reactive oxygen species (maximum turnover number, 9.8), which play an important role in regulating cell apoptosis. Confocal microscopy showed that the complexes could specifically target lysosomes in cells with a Pearsons co-localization coefficient 0.76 and 0.72 after 1u2005h and 6u2005h, respectively, followed an energy-dependent cellular uptake mechanism and damaged the integrity of lysosomes. At the same time, complexes caused a marked loss of mitochondrial membrane potential.