Three novel 6-methyl-2-oxo-quinoline-3-carbaldehyde thiosemicarbazone (H-L) transition metal complexes, [Cu(H-L)NO3H2O]·NO3 (1), [Zn(H-L)NO3H2O]·NO3 (2) and [CoL2] (3), were synthesized. In vitro antitumor screening revealed that complex 1 exhibited better inhibitory activities than the commercial anticancer drug cisplatin against SK-OV-3 and MGC80-3 tumor cell lines, with IC50 values of 10.35 ± 1.26 μM and 10.17 ± 0.95 μM, respectively. All three complexes showed low cytotoxicity toward the normal human liver HL-7702 cells compared with cisplatin. Their binding properties to DNA were investigated by various methods. It was found that the complexes interacted with DNA mainly through intercalation, and their binding affinities ranked in the order of 3 > 1 > 2. Complex 1 induced the highest apoptosis rate of MGC80-3 cells, and it caused cell arrest in the S phase according to flow cytometry. Further experiments confirmed that complex 1 triggered MGC80-3 cells apoptosis via a mitochondrial dysfunction pathway.

A novel strategy for screening the enzyme inhibitors from the natural products by capillary electrophoresis (CE) with a pre column enzyme batch reactor prepared by magnetic microsphere (MB)-gold nanoparticles (AuNPs) is reported. The enzyme batch reactor was prepared by immobilizing the enzymes on the MB conjugated AuNPs (MB-AuNPs). To demonstrate this strategy, xanthine oxidase (XOD) was employed as a model for the activity of the enzyme, inhibition study, and inhibitor screening. With the developed CE method, the enzyme activity was determined by the quantification of the peak area of the product. Enzyme inhibition can be read out directly from the reduced peak area of product in comparison to a reference electropherogram obtained in the absence of any inhibitor. A statistical parameter Z‘ factor was recommended for evaluation of the accuracy of a drug screening system. In the present study, it was calculated to be 0.7, implying a good accuracy. The screening of two natural extracts from Cortex Phellodendri and Rhizoma Galangae showed that they were positive for XOD inhibition by the present method. Using this immobilized enzyme technology combined with CE separation not only provides the advantages such as convenience, rapidity and low cost, but also provides a new platform for discovering enzyme-inhibitor drug lead compounds.

•Four μ2-Cl bridged dinuclear Zn/Mn complexes of isoquinoline derivatives were synthesized.•The complexes exhibited considerable cytotoxicity against human tumor cells.•The antitumor activity was achieved via DNA damage-mediated mitochondrial pathway.Four μ2-Cl bridged dinuclear metal complexes with isoquinoline ligands, (MPDQ)2Zn2Cl4 (1) (MPDQ = 4.5-methylenedioxy-1-pyridinedihydroisoquinoline), (PYP)2Zn2Cl4 (2) (PYP = 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline), (MPDQ)2Mn2Cl4 (3),and (PYP)2Mn2Cl4 (4) were synthesized and characterized. All complexes exhibited strong proliferation inhibition activity against various cancer cells. The underlying molecular mechanisms through which they caused the cancer cell death were also elucidated. Induction of apoptosis in MGC-803 cells by complex 2 was evidenced by annexin V+/PI− detection and DiD/DAPI staining assay. Further investigation revealed that complex 2 was able to induce intrinsic pathway-dependent apoptosis in cancer cells by triggering DNA damage which was caused by the overproduction of reactive oxygen species. Based on these studies, we suggest that Zn(II) complexes containing isoquinoline ligands can be developed as candidates for anti-cancer chemotherapeutics.Four μ2-Cl bridged dinuclear Zn(II)/Mn(II) complexes with isoquinoline derivatives were synthesized and exhibited high cytotoxicity against various tumor cells with certain selectivity to tumor and normal cells, which induced intrinsic pathways-dependent apoptosis in cancer cells by triggering DNA damage which was caused by the reactive oxygen species (ROS) overproduction.Download high-res image (83KB)Download full-size image

A new iron(III) complex with 5,7-dichloro-2-methyl-8-quinolinol (HClMQ) as ligands, i.e., [Fe(ClMQ)2Cl] (1), was synthesized and evaluated for its anticancer activity. Compared to the HClMQ ligand, complex 1 showed a higher cytotoxicity towards a series of tumor cell lines, including Hep-G2, BEL-7404, NCI-H460, A549, and T-24, with IC50 values in the range of 5.04–14.35 μM. Notably, the Hep-G2 cell line was the most sensitive to complex 1. Mechanistic studies indicated that complex 1 is a telomerase inhibitor targeting c-myc G-quadruplex DNA and can trigger cell apoptosis via inducing cell cycle arrest and DNA damage.

A novel multifunctional aggregation-induced emission (AIE) nanoaggregate for targeted imaging and enzyme-triggered chemotherapy was successfully fabricated via a one-step assembly. In this system, a quaternary ammonium-modified tetraphenylethene derivative (QA-TPE) acted as the AIE fluorophore as well as the chemotherapeutic agent, and a water-soluble acidic polysaccharide, hyaluronic acid (HA) acted as the aggregation-inducing scaffold, AIE turn-on agent, and targeting agent for CD44 receptor-mediated cancer cells. More importantly, HA endowed the QA-TPE/HA nanoaggregate both good biocompatibility and hysteretic chemotherapy activity, which were achieved by controlling the release of QA-TPE using the endogenous HAase in CD44 receptor-mediated cancer cells.

Two rhodium(III) complexes (Rh(OQ)3 (1) and Rh(BrQ)2(CH3OH)Cl (2), HOQ = 8-hydroxyquinoline, HBrQ = 5-bromo-8-hydroxyquinoline) of 8-hydroxylquinoline were synthesized and characterized. By MTT assay, the in vitro cytotoxicity of complexes 1 and 2, compared with HOQ, HBrQ and cisplatin, was evaluated towards a series of tumor cell lines as well as the normal liver cell line HL-7702. Complexes 1 and 2 showed higher cytotoxicity against the tested tumor cell lines than the corresponding ligands, among which T-24 was the most sensitive cell line for complexes 1 and 2 (IC50 = 13.42 μM for 1, 18.91 μM for 2). Compared with cisplatin, complex 1 exhibited higher cytotoxicity against T-24 cells but lower cytotoxicity against HL-7702(IC50 = 15.93 μM). Considering the better cytotoxicity of complex 1 than complex 2 against T-24 cells, the underlying anticancer molecular mechanisms were also investigated. DNA interaction studies revealed that complex 1 interacted with ct-DNA mainly via an intercalative binding mode. Further investigation of intracellular mechanisms revealed that complex 1 caused G2 phase cell cycle arrest and induced T-24 cell apoptosis in a dose-dependent mode. Targeting the mitochondrial pathway, the apoptotic mechanism in T-24 cells treated with 1 was studied by ROS detection, intracellular Ca2+ concentration measurements and caspase-9/3 activity assay, which suggested that complex 1 induced T-24 cell apoptosis by the disruption of mitochondrial-related mechanisms.

Three cobalt(II) complexes, [Co(NOQ)2(C5H5N)2]C2H5OH (1), [Co(BrQ)2(C5H5N)2] (2) and [Co(NQ)2(C5H5N)2] (3) (NOQ = 5-nitro-8-hydroxyquinoline, BrQ = 5-bromo-8-hydroxyquinoline, NHQ = 2-amino-8-hydroxyquinoline), were synthesized and characterized. Their in vitro cytotoxicity against T-24, BEL-7404, HepG2, HeLa, MGC-803, SKOV-3, HL-7702 and WI-38 cell lines was evaluated. Complexes 1–3 exhibited the highest proliferation inhibition activity against the T-24 tumor cell line with IC50 values in the range between 7.00 and 16.70 μM. They also displayed selectivity towards T-24 tumor cell lines compared to the normal liver cell line HL-7702 and human fetal lung fibroblast WI-38 cell line. The action mechanism of complex 1 was investigated. It caused apoptotic death of the T-24 cells via G1 cell cycle arrest. Further investigation revealed that complex 1 induced overproduction of reactive oxygen species, which led to mitochondrion-mediated apoptosis. DNA binding studies suggested that intercalation might be the most probable binding mode of the Co(II) complexes with ct-DNA.

The construction of advanced phototherapy systems with high therapeutic efficacy toward cancer and low side effects, especially targeted species, is highly desirable. Herein, we developed one kind of water-soluble hyaluronic acid–hybridized polyaniline nanoparticles (HA–PANI NPs) as a nanoplatform for photothermal therapy (PTT) with targeted specificity of a CD44-mediated cancer cell. The water-soluble HA–PANI NPs were fabricated by one-step oxidative polymerization using aniline as a polymerizable monomer and HA as a stabilizer and targeted agent, where non-covalent electrostatic interaction between the negatively charged polymer HA and the cationic polymer PANI drives the formation of HA–PANI NPs. It was demonstrated that approximately spherical HA–PANI NPs are well-dispersed in aqueous solutions, with average hydrodynamic diameters of around 100 nm. Besides, HA–PANI NPs have negligible cytotoxicity in vitro, which facilitates biomedical applications with low toxicity. We studied the in vitro photothermal cell-killing efficacy of HA–PANI NPs by MTT assay and confocal microscopy measurement. The results reveal that HA–PANI NPs can selectively kill the cancer cells of HeLa and HCT-116 cells rather than normal cells of HFF cells upon exposure to a NIR 808 nm laser. The efficient intracellular intake of the HA–PANI NPs by both HeLa and HCT-116 cells are observed, confirming their targeting ability for CD44-overexpressing cancer cells. Furthermore, the results of in vivo photothermal ablation of tumors show excellent treatment efficacy, indicating that the HA–PANI NPs can be considered as an extremely promising nanoplatform for targeted PTT of cancer.

Two G-quadruplex ligands [Pt(La)(DMSO)Cl] (Pt1) and [Pt(Lb)(DMSO)Cl] (Pt2) have been synthesized and fully characterized. The two complexes are more selective for SK-OV-3/DDP tumor cells versus normal cells (HL-7702). It was found that both Pt1 and Pt2 could be a telomerase inhibitor targeting G-quadruplex DNA. This is the first report demonstrating that telomeric, c-myc, and bcl-2 G-quadruplexes and caspase-3/9 preferred to bind with Pt2 rather than Pt1, which also can induce senescence and apoptosis. The different biological behavior of Pt1 and Pt2 may correlate with the presence of a 6-hydroxyl group in Lb. Importantly, Pt1 and Pt2 exhibited higher safety in vivo and more effective inhibitory effects on tumor growth in the HCT-8 and NCI-H460 xenograft mouse model, compared with cisplatin. Taken together, these mechanistic insights indicate that both Pt1 and Pt2 display low toxicity and could be novel anticancer drug candidates.

Extremely sensitive and accurate measurements of protein markers for early detection and monitoring of diseases pose a formidable challenge. Herein, we develop a new type of amplified fluorescence polarization (FP) aptasensor based on allostery-triggered cascade strand-displacement amplification (CSDA) and polystyrene nanoparticle (PS NP) enhancement for ultrasensitive detection of proteins. The assay system consists of a fluorescent dye-labeled aptamer hairpin probe and a PS NP-modified DNA duplex (assistant DNA/trigger DNA duplex) probe with a single-stranded part and DNA polymerase. Two probes coexist stably in the absence of target, and the dye exhibits relatively low FP background. Upon recognition and binding with a target protein, the stem of the aptamer hairpin probe is opened, after which the opened hairpin probe hybridizes with the single-stranded part in the PS NP-modified DNA duplex probe and triggers the CSDA reaction through the polymerase-catalyzed recycling of both target protein and trigger DNA. Throughout this CSDA process, numerous massive dyes are assembled onto PS NPs, which results in a substantial FP increase that provides a readout signal for the amplified sensing process. Our newly proposed amplified FP aptasensor enables the quantitative measurement of proteins with the detection limit in attomolar range, which is about 6 orders of magnitude lower than that of traditional homogeneous aptasensors. Moreover, this sensing method also exhibits high specificity for target proteins and can be performed in homogeneous solutions. In addition, the suitability of this method for the quantification of target protein in biological samples has also been shown. Considering these distinct advantages, the proposed sensing method can be expected to provide an ultrasensitive platform for the analysis of various types of target molecules.

Three water-soluble ruthenium(II) complexes with chiral 4-(2,3-dihydroxypropyl)-formamide oxoaporphine (FOA) were synthesized and characterized. It was found that these ruthenium(II) complexes exhibited considerable in vitro anticancer activities and that they were the effective stabilizers of telomeric and G-quadruplex-DNA (G4-DNA) in promoter of c-myc, which acted as a telomerase inhibitor targeting G4-DNA and induced cell senescence and apoptosis. Interestingly, the in vitro anticancer activity of 6 (LC-003) was higher than those of 4 (LC-001) and 5 (LC-002), more selective for BEL-7404 cells than for normal HL-7702 cells, and preferred to activate caspases-3/9. The different biological behaviors of the ruthenium complexes could be correlated with the chiral nature of 4-(2,3-dihydroxypropyl)-formamide oxoaporphine. More significantly, 6 exhibited effective inhibitory on tumor growth in BEL-7402 xenograft mouse model and higher in vivo safety than cisplatin. These mechanistic insights indicate that 6 displays low toxicity and can be a novel anticancer drug candidate.

•The Pt(II) complexes exhibited enhanced cytotoxicity toward tumor cells vs ligand.•Apoptosis is caused by the Pt(II) complexes via a mitochondrial dysfunction pathway.•Their antitumor mechanism is different from p53 inhibitor pifithrin-α.•The platinum(II) complexes interact with DNA most probably by intercalation.[Pt(Q)2] (1) and [Pt(MQ)2] (2) exhibited enhanced cytotoxicity against BEL-7404, Hep-G2, NCI–H460, T-24, A549 tumor cells but low cytotoxicity on normal HL-7702 cells. 1 and 2 could cause the cell cycle arrest in G2 and S phase, respectively. While pifithrin-α, a specific p53 inhibitor, induced cell cycle arrest in G1 phase. Although 1, 2 and pifithrin-α caused serious inhibition on p53, 1 and 2 significantly cause the loss of mitochondrial membrane potential and increase of the reactive oxygen species level, cytochrome c, apaf-1 and caspase-3/9 ratio in BEL-7404 cells. 1 and 2 may trigger the cell apoptosis through a mitochondrial dysfunction pathway whereas pifithrin-α does not. The interactions of 1 and 2 with DNA are most probably via an intercalation.

•One platinum(II) complex with phenanthrolin derivative was synthesized.•The platinum(II) complex exhibited selective cytotoxicity toward tumor cells.•Its antitumor activity was achieved via inhibiting telomerase activity.•Its mechanism is interaction c-myc quadruplex and activation of caspase-3/9.A new platinum(II) complex of [PtII(L) (pn)]Cl·2H2O (1) (pn = 1,3-propanediamine) with 2-(4-methoxy-phenyl)imidazo [4,5-f]-[1,10]phenanthrolin (H-L) was synthesized and characterized. In complex 1, the platinum adopts a four-coordinated square planar geometry. Complex 1 exhibited selective cytotoxicity against NCI–H460, BEL-7402, SK-OV-3, SK-OV-3/DDP and HeLa cell lines with IC50 values in the micromolar range (9.7–35.8 μM), but low cytotoxicity toward normal human liver HL-7702 cells. Complex 1 caused HeLa cell cycle arrest at S phase and it induced HeLa apoptosis by the activation of caspase-3/9. Various experiments showed that complex 1 preferred to bind with G-quadruplex in c-myc. Taken together, we found that complex 1 exerted its antitumor activity mainly via inhibiting telomerase by interaction with c-myc quadruplex and activation of caspase-3/9.One platinum(II) complex with phenanthrolin derivative was synthesized. It exhibited selective cytotoxicity toward tumor cells achieved via inhibiting telomerase activity by interaction c-myc quadruplex and activation of caspase-3/9.

Complexes of yttrium(III) and dysprosium(III) with the traditional Chinese medicine active ingredient oxoglaucine (OG), namely [Y(OG)2(NO3)3]·CH3OH (1) and [Dy(OG)2(NO3)3]·H2O (2), were synthesized and characterized by elemental analysis, IR, ESI-MS, 1H and 13C NMR as well as single-crystal X-ray diffraction analysis. In vitro the complexes exhibited higher anticancer activity than the free ligand OG against the tested cancer cell lines. Among the tested cell lines, HepG2 is the most sensitive to the complexes. Complex 2 can trigger DNA damage in HepG2 cells, resulting in cell cycle arrest in the S phase and leading to cell apoptosis. The S phase cell-cycle arrest is caused via the ATM (ataxia-telangiectasia mutated)-Chk2-Cdc25A pathway. Chk2 is phosphorylated and activated in an ATM-dependent manner. It, in turn, phosphorylates Cdc25A phosphatise on serine124, causing the inactivation of Cdc25A in ubiquitin-mediated proteolytic degradation. The cyclin-Cdk complexes of the S phase could also be inhibited by limited supply of cyclins A and E. This irreversible cell cycle arrest process ultimately induces mitochondria-involved apoptotic cell death via the activation of Bcl-2 protein. Complex 2 effectively inhibited tumour growth in the BEL-7402 xenograft mouse model and exhibited higher safety in vivo than cisplatin.

A new anthracycline derivative, anthracene-9-imidazoline hydrazone (9-AIH), was synthesized and selected as an antitumor ligand to afford a copper(II) complex of 9-AIH, cis-[CuIICl2(9-AIH)] (1). Complex 1 was structurally characterized by IR, elemental analysis, ESI-MS and single crystal X-ray diffraction analysis. By MTT assay, it was revealed that 1 showed overall a higher in vitro cytotoxicity than 9-AIH towards a panel of human tumour cell lines, with IC50 values from 0.94–3.68 μM, in which the BEL-7404 cell line was the most sensitive to 1. By spectral analyses and gel electrophoresis, the DNA binding affinity of 9-AIH and 1 was determined. 9-AIH was suggested to bind with DNA in an intercalative mode, with a quenching constant of 1.04 × 104 M−1 on the EB–DNA complex. While for 1, both intercalative and covalent binding modes were suggested. By flow cytometry, 1 was found to block the cell cycle of BEL-7404 cells in a dose-dependent mode, in which it induced the G2/M phase arrest at 0.5 μM and induced the S phase arrest at higher concentrations of 1.0 or 2.0 μM. From the cellular morphological observations under different fluorescence probe staining, a dose-dependent manner of 1 to induce cell apoptosis in the late stage was suggested. Comparatively, equivalent apoptotic cells, respectively, in the early and late stages were found when incubated with 2.0 μM of 9-AIH. The mitochondrial membrane potential measured by JC-1 staining and the ROS generation in cells detected using a DCFH-DA probe suggested that the cell apoptosis induced by 1 might undergo the ROS-related mitochondrial pathway. Accordingly, the mutant p53 expression was found to be suppressed and the caspase cascade (caspase-9/3) was consequently activated by 1. This action mechanism for 1 in the BEL-7404 cells was unique and was not found in the presence of 9-AIH under the same conditions, indicating their different antitumor mechanism. Furthermore, the in vivo acute toxicity of 1 tested on mice indicated that 1 should be a high cytotoxic antitumor agent, with the LD50 value in the range of 32–45 mg kg−1, which is much higher than that of 9-AIH. From the above results, the central Cu(II) of 1 in the coordinated mode with 9-AIH was believed to play a key role in exerting both the high cytotoxicity and the effective antitumor mechanism.

Three new copper(II) complexes of 4,5-methylenedioxy-1-pyridinedihydroisoquinoline (MPDQ), [Cu2(MPDQ)2Cl4] (1), [Cu(MPDQ)(H2O)(SO4)] (2), and [Cu2(MPDQ)2(C2O4)(ClO4)2] (3) were synthesized and characterized. They exhibit enhanced cytotoxicity against the tested human tumor cells BEL-7404, SK-OV-3, HepG2, A549, A375, MGC-803 and NCI-H460 compared to MPDQ and the corresponding copper(II) salts with IC50 values of 1.41–34.54 μM. Complex 1 can induce apoptotic death in BEL-7404 by S cell cycle arrest and complex 1-induced apoptosis, which were involved in an intrinsic pathway, including up-regulating P53 and down-regulating Bcl-2 and mitochondrial membrane potential, leading to sequential activation of caspase-9 and caspase-3. ICP-MS testing implied that the copper(II) complexes could enter cells and DNA was one important target; DNA binding studies revealed that intercalation might be the most probable binding mode of the new Cu(II) complexes with ct-DNA.

A simple, label-free and amplified colorimetric assay strategy based on a novel enzyme-responsive DNAzyme cascade has been developed for assay of ribonuclease H activity and inhibition. This novel strategy improved the detection sensitivity by two orders of magnitude over the previously reported methods.

A new zinc(II) complex (1) of 5-bromo-8-hydroxyquinoline (HBrQ) was prepared and structurally characterized using IR, ESI-MS, elemental analysis, 1H and 13C NMR, as well as single crystal X-ray diffraction analysis. The DNA binding study on complex 1, which was performed using UV-vis, fluorescence and circular dichroism (CD) spectral analyses, suggested that complex 1 interacts with ct-DNA mainly via an intercalative binding mode. The in vitro cytotoxicity of complex 1, compared with Zn(OAc)2·H2O, HBrQ and cisplatin, was screened against a series of tumor cell lines as well as the normal liver cell line HL-7702 using the MTT assay. Complex 1 showed much higher cytotoxicity than Zn(OAc)2·H2O and HBrQ against most of the tumor cell lines, in which BEL-7404 was the most sensitive tumor cell line towards 1, with an IC50 value of 8.69 ± 0.04 μM. Complex 1 was found to greatly induce cell cycle arrest in the BEL-7404 cells at the G2 phase, and consequently to induce cell apoptosis in a dose-dependent mode, which is suggested by the cell apoptosis analysis via the Hoechst 33258 and AO/EB staining assays. Targeting the mitochondria pathway due to the redox activity of Zn, the apoptotic mechanism in the BEL-7404 cells treated by 1 was investigated using reactive oxygen species (ROS) detection, intracellular calcium concentration measurement and caspase-9/3 activity assay, which showed that the cell apoptosis induced by 1 was closely related to the loss of mitochondrial membrane potential, ROS production and enhancement of intracellular [Ca2+], which trigger caspase-9/3 activation via the mitochondrial dysfunction pathway.

•Novel amplified fluorescence polarization aptasensors were developed.•The assays combined nicking enzyme signal amplification and graphene oxide enhancement.•These aptasensors exhibited higher sensitivity over traditional homogeneous aptasensors by four order of magnitude.•This assay protocol provides a new strategy for the preparation of amplified fluorescence polarization aptasensors.In this work, two different configurations for novel amplified fluorescence polarization (FP) aptasensors based on nicking enzyme signal amplification (NESA) and graphene oxide (GO) enhancement have been developed for ultrasensitive and selective detection of biomolecules in homogeneous solution. One approach involves the aptamer-target binding induced the stable hybridization between an aptamer probe and a fluorophore-labeled DNA probe linked to GO, and forms a nicking site-containing duplex DNA region due to the enhancement of base stacking. The second analytical method involves the target induced the assembly of two aptamer subunits into an aptamer-target complex, and then hybridizes with a fluorophore-labeled DNA probe linked to GO, forming a nicking site-containing duplex DNA region. The formation of the duplex DNA region in both methods triggers the NESA process, resulting in the release of many short DNA fragments carrying the fluorophore from GO, generating a significant decrease of the FP value that provides the readout signal for the amplified sensing process. By using the NESA coupled GO enhancement path, the sensitivity of the developed aptasensors can be significantly improved by four orders of magnitude over traditional aptamer-based homogeneous assays. Moreover, these aptasensors also exhibit high specificity for target molecules, which are capable of detecting target molecule in biological samples. Considering these qualities, the proposed FP aptasensors based NESA and GO enhancement can be expected to provide an ultrasensitive platform for amplified analysis of target molecules.

In this paper, we present a new and facile one-step method for the fabrication of a water-soluble graphene–phthalocyanine (GR–Pc) hybrid material by simply sonicating GR with a hydrophilic Pc, tetrasulfonic acid tetrasodium salt copper phthalocyanine (TSCuPc). In the resultant hybrid material, TSCuPc is coated on the skeleton of pristine GR via non-covalently π–π interaction, detailedly characterized by UV-vis/Raman spectra, X-ray photoelectron spectroscopy (XPS), etc. The obtained GR–Pc hybrid (GR–TSCuPc) is applied for photothermal therapy (PTT) and photodynamic therapy (PDT). In this PTT/PDT system, both GR and TSCuPc operate as multifunctional agents: GR acts as a photosensitizer carrier and PTT agent, while TSCuPc acts as a hydrophilic PDT agent. Furthermore, the results of cell viability show that the phototherapy effect of GR–TSCuPc is observably higher than that of free TSCuPc, indicating that combined noninvasive PTT/PDT exhibits better anti-cancer efficacy in vitro. Such results highlight that this work provide a facile method to develop efficacious dual-modality carbon nanoplatform for developing cancer therapeutics.

The biomedical applications of carbon nanomaterials, especially integrating noninvasive photothermal therapy (PTT) and photodynamic therapy (PDT), into a single system have enormous potential in cancer therapy. Herein, we present a novel and facile one-step method for the preparation of water-soluble single-walled carbon nanohorns (SWNHs) and metal phthalocyanines (MPc) hybrid for PTT and PDT. The hydrophilic MPc, tetrasulfonic acid tetrasodium salt copper phthalocyanine (TSCuPc), is coated on the surface of SWNHs via noncovalent π–π interaction using the sonication method. In this PTT/PDT nanosystem, SWNHs acts as a photosensitizer carrier and PTT agent, while TSCuPc acts as a hydrophilic and PDT agent. The EPR results demonstrated that the generated reactive oxygen species (ROS) not only from the photoinduced electron transfer process from TSCuPc to SWNHs but also from SWNHs without exciting TSCuPc to its excited state. The test of photothermal conversion proved that not only do SWNHs contribute to the photothermal therapy (PTT) effect, TSCuPc probably also contributes to that when it coats on the surface of SWNHs upon exposure to a 650-nm laser. More importantly, the results of in vitro cell viability revealed a significantly enhanced anticancer efficacy of combined noninvasive PTT/PDT, indicating that the SWNHs–TSCuPc nanohybrid is a hopeful candidate material for developing an efficient and biocompatible nanoplatform for biomedical application.Keywords: metal phthalocyanine; photodynamic therapy; photothermal therapy; single-walled carbon nanohorns

•Three platinum(II) complexes of MOIP show growth inhibitions on 4 tumour cell lines.•The complexes block cell cycle at sub-G1 phase and induce apoptosis in HeLa cells.•The complexes induce and stabilize the formation of human telomeric G-quadruplex DNA.•The 2-methoxy ligand with lower steric hindrance has better DNA binding affinity.Three platinum(II) complexes, including 2-(2-methoxy-phenyl) imidazo [4,5-f]-[1,10] phenanthroline, 2-(3-methoxy-phenyl) imidazo [4,5-f]-[1,10] phenanthroline and 2-(4-methoxy-phenyl) imidazo [4,5-f]-[1,10] phenanthroline, were synthesised and structurally characterised. In complexes 1–3, the platinum centre adopts a four-coordinate square planar geometry. In the MTT assay, these complexes exhibited considerable cytotoxicities against the SPC-A-2, MGC80-3, BEL-7404 and HeLa human tumour cell lines, with IC50 values in the range of 4.7 ± 0.8 to 23.3 ± 0.4 μM, and lower cytotoxicities towards the HL-7702 human normal liver cell line. By flow cytometry analyses, the HeLa cells treated with complexes 1–3 for 72 h exhibited DNA damage at the sub-G1 phase with a dose-dependent effect resulting in the blockage of cell cycle at sub-G1 phase, which might contribute to the cell apoptosis observed in HeLa cells. From the results of the CD, UV–vis and FID spectral analyses, complexes 1–3 showed good binding affinity with human telomeric G-quadruplex DNA. It suggested the potential inhibition on the telomerase activity, which should be a key antitumour mechanism for complexes 1–3. Furthermore, complex 1 with 2-substituted MOIP ligand, which may have lower steric hindrance for DNA intercalation, showed higher G-quadruplex DNA binding affinity than complexes 2 and 3. This was supported by the results from cell growth inhibition and cell apoptosis induction.Three platinum(II) complexes 1–3 bearing with 2-(methoxy-phenyl)imidazo[4,5-f]-[1,10] phenanthroline ligands showed higher cytotoxicities against SPC-A-2, MGC80-3, BEL-7404 and HeLa human tumour cell lines with IC50 values in the range of 4.7–23.3 μM than the HL-7702 normal liver cell line. They significantly induced cell apoptosis and blocked the cell cycle at sub-G1 phase in HeLa cells, in which the 2-methoxy substituted ligand showed the better cell apoptosis induction. Complexes 1–3 also suggested potent inhibitions on telomerase activity due to their higher binding affinities with human telomeric G-quadruplex DNA than with double helix DNA.

•A versatile sensing platform for DNA MTase was proposed.•The detection based on multiwalled carbon nanotube signal amplification and fluorescence polarization.•The nanosensor exhibited very high sensitivity and specificity for DNA MTase detection.•This design provides a new method for the preparation of amplified fluorescence polarization sensor.A versatile sensing platform based on multiwalled carbon nanotube (MWCNT) signal amplification and fluorescence polarization (FP) is developed for the simple and ultrasensitive monitoring of DNA methyltransferase (MTase) activity and inhibition in homogeneous solution. This method uses a dye-labeled DNA probe that possess a doubled-stranded DNA (dsDNA) part for Mtase and its corresponding restriction endonuclease recognition, and a single-stranded DNA part for binding MWCNTs. In the absence of MTase, the dye-labeled DNA is cleaved by restriction endonuclease, and releases very short DNA carrying the dye that cannot bind to MWCNTs, which has relatively small FP value. However, in the presence of MTase, the specific recognition sequence in the dye-labeled DNA probe is methylated and not cleaved by restriction endonuclease. Thus, the dye-labeled methylated DNA product is adsorbed onto MWCNTs via strong π–π stacking interactions, which leads to a significant increase in the FP value due to the enlargement of the molecular volume of the dye-labeled methylated DNA/MWCNTs complex. This provides the basic of a quantitative measurement of MTase activity. By using the MWCNT signal amplification approach, the detection sensitivity can be significantly improved by two orders of magnitude over the previously reported methods. Moreover, this method also has high specificity and a wide dynamic range of over five orders of magnitude. Additionally, the suitability of this sensing platform for MTase inhibitor screening has also been demonstrated. This approach may serve as a general detection platform for sensitive assay of a variety of DNA MTases and screening potential drugs.

In this work, a novel carbon nanotube (CNT)-based multicolor fluorescent peptide nanoprobe is developed for rapid, sensitive, and multiplex detection of cancer-related proteases in homogeneous solution. To prepare the nanoprobe, three peptide substrates, each labeled at the C-terminal with a fluorescent dye (i.e., fluorescein isothiocyanate (FITC), cyanine dye Cy3, cyanine dye Cy5), that respond to one of three different proteases are co-conjugated to the surface of CNTs. This conjugation brings the dyes into the proximity of the CNT surface, which leads to significantly quenched fluorescence due to highly efficient long-range energy transfer from the dyes to CNTs. However, upon incubation with the targeted proteases, specific peptide cleavage occurs and releases the dyes from the CNT surface, which results in the fluorescence recovery that provides the basis for a quantitative measurement of protease activity. With the use of three cancer-related proteases, matrix metalloproteinase-7 (MMP-7), matrix metalloproteinase-2 (MMP-2), and urokinase-type plasminogen activator (uPA), as the proof-of-concept analytes, the nanoprobe could simultaneously detect these proteases with high sensitivity and specificity. The limits of detection for this method are obtained in the range 0.5 pg mL−1 to 500 pg mL−1, which are two orders of magnitude lower than many previously reported methods. Moreover, the suitability of this CNT-based sensing platform for complex biological sample analysis has also been demonstrated. This approach holds great promise as a routine tool for the high-throughput screening of proteases in proteomics and clinical diagnostics.

A novel fluorescence polarization (FP) nanosensor based on λ exonuclease cleavage reaction and FP enhancement effect of gold nanoparticles (AuNPs) has been developed for the detection of T4 polynucleotide kinase activity and inhibition. This FP sensor exhibits higher detection sensitivity over traditional fluorescence sensors by two orders of magnitude.

Highly sensitive detection of proteins is essential to biomedical research as well as clinical diagnosis. Here, we develped a novel label-free colorimetric aptasensor based on nicking enzyme assisted signal amplification and DNAzyme amplification for highly sensitive detection of protein. The system consists of a hairpin DNA probe carrying an aptamer sequence for target, a G-riched DNA probe containing two G-riched DNAzyme segments and the recognition sequence as well as cleavage site for nicking enzyme, a blocker DNA, and the nicking enzyme. The hybridization of the G-riched DNA with the blocker DNA prohibits the formation of the activated DNAzymes in the absence of target. Upon addition of target to the system, the hairpin probe is opened by the specific recognition of the target to its aptamer. The open hairpin probe hybridizes with a G-riched DNA and forms a DNA duplex, which triggers the selective cleavage of the G-riched DNA probe by nicking enzyme, leading to the release of the aptamer–target complex and the G-riched DNAzyme segments. The released open hairpin probe then hybridizes with another G-riched DNA probe, and the cycle starts anew, resulting in the continuous cleavage of the G-riched DNA probes, generating a much of G-riched DNAzyme segments. The G-riched DNAzyme segments interact with hemin and generates the activated DNAzyme that can catalyze the H2O2-mediated oxidation of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS2–) to the colored ABTS•–, thus providing the amplified colorimetric detection of target. With the use of thrombin (Tb) as a proof-of-principle analyte, this sensing platform can detect Tb specifically with a detection limit as low as 1.5 pM, which is at least 4 orders of magnitude lower over the unamplified colorimetric assay. Moreover, the assay does not involve any chemical modification of DNA, which is simple and low-cost. This sensing platform provides a promising approach for the amplified analysis of target molecules.

Six new platinum(II) complexes with mono-aminophosphonate ester were synthesized and characterized by elemental analysis, 1H NMR, ESI-MS as well as single crystal X-ray diffraction analysis. They are mononuclear structures. In all the crystal structures of complexes 1–6, the platinum centre adopts an approximately square-planar geometry, which were found to possess excellent solubility in both organic solvents and water and exhibit considerable cytotoxicity against MG-63, SK-OV-3 and HepG2 cell lines, but low cytotoxicity towards normal human liver cell HL-7702. In contrast to cisplatin, their antitumour activities are achieved through the induction of cell apoptosis by G1 cell-cycle arrest.Graphical abstractSix platinum(II) complexes with mono-aminophosphonate ester were synthesized. They are soluble in organic solvents and water, exhibited considerable cytotoxicity achieved through the cell apoptosis mainly by G1 cell-cycle arrest.Highlights► Six platinum(II) complexes with mono-aminophosphonate ester were synthesized. ► The platinum(II) complexes were soluble in both organic solvents and water. ► They exhibited considerable cytotoxicity and induced cell-cycle arrest at G1 phase.

•Six platinum(II) complexes with mono-aminophosphonate ester were synthesized.•The platinum(II) complexes were soluble in both organic solvents and water.•Their antitumor activities were achieved via cell apoptosis and G1cell cycle arrest.New platinum(II) complexes containing aminophosphonate ester were synthesized and fully characterized, which were found to possess better solubility in both organic solvents and water than cisplatin. These platinum(II) complexes exhibited considerable cytotoxicity against tumor cells MG-63, SK-OV-3, HepG2, BEL-7404 and low cytotoxicity to normal human liver cells HL-7702. Their antitumor activities were achieved through the induction of cell apoptosis and the cell cycle arrest at G1 phase. The electrophoretic mobility studies and CD spectral analysis revealed that the binding mode of complex 6 to DNA might be different from that of cisplatin.Six platinum(II) complexes with mono-aminophosphonate ester were synthesized. They are soluble in organic solvents and water, exhibited considerable cytotoxicity achieved through the cell apoptosis and G1 cell cycle arrest.

This work reports the design of a novel peptide antigen-based multicolor fluorescent gold nanoparticles (AuNP) immunosensor for multiplex detection of peptides and proteins in homogeneous solution. The three involved peptides were first labeled with three different fluorescent dyes at their N-terminus, and the dye-labeled peptide antigens were then reacted with AuNPs functionalized with three relevant antibodies to obtain a multicolor fluorescent AuNPs immunosensor. In the presence of target molecules, the dye-labeled peptide antigens were released from the AuNPs surface because of competitive immunoreactions, generating higher fluorescence that provided signal readout for the immunosensing process. Importantly, the large surface area of the AuNPs allows simultaneous quenching of multiple peptide antigens labeled with different dyes via the binding with AuNPs-conjugated antibodies, leading to a multicolor nano-immunosensor for the detection of multiple targets in same solution. Furthermore, the application of this AuNPs-based multicolor fluorescent immunosensor for complex biological sample analysis is also demonstrated. This approach offers high sensitivity and selectivity, and promises an efficient platform for low-cost multiplexed immunoassay of biomolecules.

We have developed an amplified chemiluminescence turn-on sensing platform that relies on single-walled carbon nanotubes for ultrasensitive DNA detection. This new type of assay exhibits higher detection sensitivity over traditional biosensors by three orders of magnitude and high specificity for the target molecules.

We have developed an amplified chemiluminescence aptasensor based on bi-resonance energy transfer on gold nanoparticles and exonuclease III-catalyzed target recycling. This assay exhibits high detection sensitivity over traditional biosensors in three orders of magnitude and high specificity for target molecules.

We have developed an amplified fluorescence polarization aptasensor that relies on aptamer structure-switching-triggered nanoparticles (NPs) enhancement for biomolecules detection. This new type of assay exhibits higher detection sensitivity over traditional homogeneous aptasensors by two orders of magnitude and high specificity for target molecules.

The alkaloid oxoglaucine (OG), which is a bioactive component from traditional Chinese medicine (TCM), was synthesized by a two-step reaction and used as the ligand to react with transition metal salts to give four complexes: [OGH][AuCl4]·DMSO (1), [Zn(OG)2(H2O)2](NO3)2 (2), [Co(OG)2(H2O)2](ClO4)2 (3), and [Mn(OG)2(H2O)2](ClO4)2 (4). The crystal structures of the metal complexes were confirmed by single crystal X-ray diffraction. Complex 1 is an ionic compound consisting of a charged ligand [OGH]+ and a gold complex [AuCl4]−. Complexes 2–4 all have similar structures (inner-spheres), that is, octahedral geometry with two OG coordinating to one metal center and two aqua ligands occupying the two apical positions of the octahedron, and two NO3– or ClO4– as counteranions in the outer-sphere. The complexation of OG to metal ion was confirmed by ESI-MS, capillary electrophoresis and fluorescence polarization. The in vitro cytotoxicity of these complexes toward a various tumor cell lines was assayed by the MTT method. The results showed that most of these metal–oxoglaucine complexes exhibited enhanced cytotoxicity compared with oxoglaucine and the corresponding metal salts, with IC50 values ranging from 1.4 to 32.7 μM for sensitive cancer cells, which clearly implied a positive synergistic effect. Moreover, these complexes appeared to be selectively active against certain cell lines. The interactions of oxoglaucine and its metal complexes with DNA and topoisomerase I were investigated by UV–vis, fluorescence, CD spectroscopy, viscosity, and agarose gel electrophoresis, and the results indicated that these OG–metal complexes interact with DNA mainly via intercalation. Complexes 2–4 are metallointercalators, but complex 1 is not. These metal complexes could effectively inhibit topoisomerase I even at low concentration. Cell cycle analysis revealed that 1–3 caused S-phase cell arrest.

A series of novel oxoisoaporphine-based inhibitors (10-aminoalkylamino-1-azabenzanthrone Ar–NH(CH2)nNR1R2) of acetylcholinesterase (AChE) has been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE) and AChE-induced β-amyloid (Aβ) aggregation. The synthetic compounds exhibited high AChE inhibitory activity with IC50 values in the submicromolar range in most cases. Non-competitive binding mode was found for these derivatives by the graphical analysis of steady-state inhibition data. Moreover, all compounds exhibit significant inhibitory activity on AChE-induced Aβ aggregation with inhibitory potency from 54.5% to 93.5%. Finally, six out of twelve synthetic compounds were predicted to be able to cross the blood–brain barrier (BBB) to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. The result encourages us to study this class of compounds thoroughly and systematically.A series of novel oxoisoaporphine-based inhibitors of acetylcholinesterase has been designed, synthesized, and tested for their ability to inhibit acetylcholinesterase, butyrylcholinesterase, acetylcholinesterase-induced Aβ(1–40) aggregation and their potentiality to penetrate the blood–brain barrier.

A new nickel(II) complex with 5,7-dichloro-8-hydroxylquinoline (H–ClQ), [NiCl(ClQ)(H–ClQ)(μ-Cl)Ni(ClQ)(CH3CH2OH)(H–ClQ)]·CH3COCH3 (1), was synthesized and characterized. In solid state, 1 is consisted of a dinuclear nickel(II) complex and one acetone solvent molecule. Two Ni(II) atoms are chelated by two bidentate 5,7-dichloro-8-hydroxylquinolines and coordinated by one terminal Cl atom or ethanol ligand and one μ-Cl in a distorted octahedral coordination environment. The ESI-MS result shows that the μ-Cl bridge is easily broken in solution to give mononuclear species (omitted as ClQ–Ni complex). The IC50 values of 1 for the inhibition of the proliferation of BEL7404, SGC7901 and MCF-7 tumor cells are 13.0 ± 2.1, 15.9 ± 5.3, and 29.8 ± 9.5 μM, respectively, which exhibit significantly enhanced cytotoxicity comparing with free H–ClQ and NiCl2. The binding properties of ClQ–Ni complex to DNA were investigated by UV–Vis, fluorescence, CD spectroscopy, viscosity and agarose gel electrophoresis. The results indicate that intercalation is the most probable binding mode for ClQ–Ni complex to DNA. The ClQ–Ni complex exhibits potent TOPO I inhibition activity at 50 μM.Graphical abstractA dinuclear nickel(II) of complex [NiCl(ClQ)(H–ClQ)(μ-Cl)Ni(ClQ)(CH3CH2OH)(H–ClQ)]·CH3COCH3 (1) was found to display significantly enhanced cytotoxicity versus free H–ClQ and NiCl2.Highlights► A ClQ–Ni complex [NiCl(ClQ)(H–ClQ)(μ-Cl)Ni(ClQ)(CH3CH2OH)(H–ClQ)]·CH3COCH3 was synthesized and fully characterized. ► This ClQ–Ni complex displays significantly enhanced cytotoxicity versus free H–ClQ and NiCl2. ► The intercalation is the most probable binding mode for ClQ–Ni complex to DNA.

We have developed a highly sensitive and selective fluorescence polarization assay method based on the specificity of the DNA cleavage reaction with the enhancement of gold nanoparticles (AuNPs) for assaying endonuclease activity and inhibition. This assay can detect EcoRI endonuclease down to 5.0 × 10−4 U mL−1 with a detection range from 5.0 × 10−4 to 10 U mL−1.

DNA cleavage by endonucleases plays an important role in many biological events such as DNA replication, recombination, and repair and is used as a powerful tool in medicinal chemistry. However, conventional methods for assaying endonuclease activity and inhibition by gel electrophoresis and chromatography techniques are time-consuming, laborious, not sensitive, or costly. Herein, we combine the high specificity of DNA cleavage reactions with the benefits of quantum dots (QDs) and ultrahigh quenching abilities of inter- and intramolecular quenchers to develop highly sensitive and specific nanoprobes for multiplexed detection of endonucleases. The nanoprobe was prepared by conjugating two sets of DNA substrates carrying quenchers onto the surface of aminated QDs through direct assembly and DNA hybridization. With this new design, the background fluorescence was significantly suppressed by introducing inter- and intramolecular quenchers. When these nanoprobes are exposed to the targeted endonucleases, specific DNA cleavages occur and pieces of DNA fragments are released from the QD surface along with the quenchers, resulting in fluorescence recovery. The endonuclease activity was quantified by monitoring the change in the fluorescence intensity. The detection was accomplished with a single excitation light. Multiplexed detection was demonstrated by simultaneously assaying EcoRI and BamHI (as model analytes) using two different emissions of QDs. The limits of detection were 4.0 × 10–4 U/mL for EcoRI and 8.0 × 10–4 U/mL for BamHI, which were at least 100 times more sensitive than traditional gel electrophoresis and chromatography assays. Moreover, the potential application of the proposed method for screening endonuclease inhibitors has also been demonstrated. The assay protocol presented here proved to be simple, sensitive, effective, and easy to carry out.

A microchip electrophoresis method with laser induced fluorescence detection was developed for the immunoassay of phenobarbital. The detection was based on the competitive immunoreaction between analyte phenobarbital and fluorescein isothiocyanate (FITC) labeled phenobarbital with a limited amount of antibody. The assay was developed by varying the borate concentration, buffer pH, separation voltage, and incubation time. A running buffer system containing 35 mM borate and 15 mM sodium dodecyl sulfate (pH 9.5), and 2800 V separation voltage provided analysis conditions for a high-resolution, sensitive, and repeatable assay of phenobarbital. Free FITC-labeled phenobarbital and immunocomplex were separated within 30 s. The calibration curve for phenobarbital had a detection limit of 3.4 nM and a range of 8.6–860.0 nM. The assay could be used to determine the phenobarbital plasma concentration in clinical plasma sample.

An integrated microchip electrophoresis (MCE) system with online immunoreaction and laser induced fluorescence (LIF) detection has been developed for simultaneous determination of multi-analytes. In this system, the multiplexed immunoreactions between multiple antibody-immobilized glass beads with analytes and respective fluorescently labeled antigens were performed in a sample reservoir. After online incubation, the immunoreaction solution was injected into a one-way separation channel, and free fluorescently labeled antigens were separated and detected in the separation channel. With the help of glass beads, the immunocomplex can not move into the separation channel, which simplifies the separation of fluorescently labeled antigens. With the use of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ) and theophylline (Th) as proof-of-principle analytes, the one-way multiplexed immunoassay could be completed within 20 min, resulting in a response curve over the range of 4.0–400 nM for each analyte. Detection limits (S/N = 3) for the drugs tested were in the range of 1.8 × 10−9 to 2.5 × 10−9 M. Compared with the conventional immunoassays, this assay is simple, rapid, sensitive and low cost, and provides an accurate procedure for a multiplex immunoassay. The present method has been applied for the simultaneous determination of PB, PHT, CBZ and Th in human serum, which showed a promise of automated clinical application.

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone, H-PLN) was isolated from Plumbago zeylanica, the anticancer traditional Chinese medicine (TCM). Five new lanthanide(III) complexes of deprotonated plumbagin: [Y(PLN)3(H2O)2] (1), [La(PLN)3(H2O)2] (2), [Sm(PLN)3(H2O)2]⋅H2O (3), [Gd(PLN)3(H2O)2] (4), and [Dy(PLN)3(H2O)2] (5) were synthesized by the reaction of plumbagin with the corresponding lanthanide salts, in amounts equal to ligand/metal molar ratio of 3:1. The PLN–lanthanide(III) complexes were characterized by different physicochemical methods: elemental analyses, UV–visible, IR and 1H NMR and ESI-MS (electrospray ionization mass spectrum) as well as TGA (thermogravimetric analysis). The plumbagin and its lanthanide(III) complexes 1–5, were tested for their in vitro cytotoxicity against BEL7404 (liver cancer) cell lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The five PLN–lanthanide (III) complexes 1–5 effectively inhibited BEL7404 cell lines growth with IC50 values of 11.0 ± 3.5, 5.1 ± 1.3, 6.1 ± 1.1, 6.4 ± 1.3, and 9.8 ± 1.5 μM, respectively, and exhibited a significantly enhanced cytotoxicity compared to plumbagin and the corresponding lanthanide salts, suggesting a synergistic effect upon plumbagin coordination to the Ln(III) ion. The lanthanide complexes under investigation also exerted dose- and time-dependent cytotoxic activity. [La(PLN)3(H2O)2] (2) and plumbagin interact with calf thymus DNA (ct-DNA) mainly via intercalation mode, but for [La(PLN)3(H2O)2] (2), the electrostatic interaction should not be excluded; the binding affinity of [La(PLN)3(H2O)2] (2) to DNA is stronger than that of free plumbagin, which may correlate with the enhanced cytotoxicity of the PLN–lanthanide(III) complexes.Five new lanthanide(III) complexes with plumbagin (H-PLN): [Y(PLN)3(H2O)2] (1) [La(PLN)3(H2O)2] (2), [Sm(PLN)3(H2O)2]⋅H2O (3), [Gd(PLN)3(H2O)2] (4), and [Dy(PLN)3(H2O)2] (5) were synthesized and characterized. These lanthanide complexes exhibit significantly enhanced cytotoxicity to BEL7404 vs. free plumbagin, and the interactions with DNA were studied.

A rapid and sensitive microchip electrophoresis (MCE) method with laser induced fluorescence (LIF) detection has been developed for the quantification of d-tyrosine (Tyr) in biological samples. The assay was performed using a MCE-LIF system with glass/poly(dimethylsiloxane) (PDMS) hybrid microchip after pre-column derivatization of amino acids with fluorescein isothiocyanate (FITC). Chiral separation of the derivatives was achieved by cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) using γ-CD as chiral selector in the running buffer. d/l-Tyr enantiomer was well separated in less than 140 s. The limit of detection (S/N = 3) was 3.3 × 10−8 M. Using the present method, d-Tyr level in human plasma was found to vary significantly from normal humans to patients suffering from renal failure.

We have developed an amplified chemiluminescence aptasensor based on bi-resonance energy transfer on gold nanoparticles and exonuclease III-catalyzed target recycling. This assay exhibits high detection sensitivity over traditional biosensors in three orders of magnitude and high specificity for target molecules.

The construction of advanced phototherapy systems with high therapeutic efficacy toward cancer and low side effects, especially targeted species, is highly desirable. Herein, we developed one kind of water-soluble hyaluronic acid–hybridized polyaniline nanoparticles (HA–PANI NPs) as a nanoplatform for photothermal therapy (PTT) with targeted specificity of a CD44-mediated cancer cell. The water-soluble HA–PANI NPs were fabricated by one-step oxidative polymerization using aniline as a polymerizable monomer and HA as a stabilizer and targeted agent, where non-covalent electrostatic interaction between the negatively charged polymer HA and the cationic polymer PANI drives the formation of HA–PANI NPs. It was demonstrated that approximately spherical HA–PANI NPs are well-dispersed in aqueous solutions, with average hydrodynamic diameters of around 100 nm. Besides, HA–PANI NPs have negligible cytotoxicity in vitro, which facilitates biomedical applications with low toxicity. We studied the in vitro photothermal cell-killing efficacy of HA–PANI NPs by MTT assay and confocal microscopy measurement. The results reveal that HA–PANI NPs can selectively kill the cancer cells of HeLa and HCT-116 cells rather than normal cells of HFF cells upon exposure to a NIR 808 nm laser. The efficient intracellular intake of the HA–PANI NPs by both HeLa and HCT-116 cells are observed, confirming their targeting ability for CD44-overexpressing cancer cells. Furthermore, the results of in vivo photothermal ablation of tumors show excellent treatment efficacy, indicating that the HA–PANI NPs can be considered as an extremely promising nanoplatform for targeted PTT of cancer.

In this work, a novel carbon nanotube (CNT)-based multicolor fluorescent peptide nanoprobe is developed for rapid, sensitive, and multiplex detection of cancer-related proteases in homogeneous solution. To prepare the nanoprobe, three peptide substrates, each labeled at the C-terminal with a fluorescent dye (i.e., fluorescein isothiocyanate (FITC), cyanine dye Cy3, cyanine dye Cy5), that respond to one of three different proteases are co-conjugated to the surface of CNTs. This conjugation brings the dyes into the proximity of the CNT surface, which leads to significantly quenched fluorescence due to highly efficient long-range energy transfer from the dyes to CNTs. However, upon incubation with the targeted proteases, specific peptide cleavage occurs and releases the dyes from the CNT surface, which results in the fluorescence recovery that provides the basis for a quantitative measurement of protease activity. With the use of three cancer-related proteases, matrix metalloproteinase-7 (MMP-7), matrix metalloproteinase-2 (MMP-2), and urokinase-type plasminogen activator (uPA), as the proof-of-concept analytes, the nanoprobe could simultaneously detect these proteases with high sensitivity and specificity. The limits of detection for this method are obtained in the range 0.5 pg mL−1 to 500 pg mL−1, which are two orders of magnitude lower than many previously reported methods. Moreover, the suitability of this CNT-based sensing platform for complex biological sample analysis has also been demonstrated. This approach holds great promise as a routine tool for the high-throughput screening of proteases in proteomics and clinical diagnostics.

A novel fluorescence polarization (FP) nanosensor based on λ exonuclease cleavage reaction and FP enhancement effect of gold nanoparticles (AuNPs) has been developed for the detection of T4 polynucleotide kinase activity and inhibition. This FP sensor exhibits higher detection sensitivity over traditional fluorescence sensors by two orders of magnitude.

In this paper, we present a new and facile one-step method for the fabrication of a water-soluble graphene–phthalocyanine (GR–Pc) hybrid material by simply sonicating GR with a hydrophilic Pc, tetrasulfonic acid tetrasodium salt copper phthalocyanine (TSCuPc). In the resultant hybrid material, TSCuPc is coated on the skeleton of pristine GR via non-covalently π–π interaction, detailedly characterized by UV-vis/Raman spectra, X-ray photoelectron spectroscopy (XPS), etc. The obtained GR–Pc hybrid (GR–TSCuPc) is applied for photothermal therapy (PTT) and photodynamic therapy (PDT). In this PTT/PDT system, both GR and TSCuPc operate as multifunctional agents: GR acts as a photosensitizer carrier and PTT agent, while TSCuPc acts as a hydrophilic PDT agent. Furthermore, the results of cell viability show that the phototherapy effect of GR–TSCuPc is observably higher than that of free TSCuPc, indicating that combined noninvasive PTT/PDT exhibits better anti-cancer efficacy in vitro. Such results highlight that this work provide a facile method to develop efficacious dual-modality carbon nanoplatform for developing cancer therapeutics.

Complexes of yttrium(III) and dysprosium(III) with the traditional Chinese medicine active ingredient oxoglaucine (OG), namely [Y(OG)2(NO3)3]·CH3OH (1) and [Dy(OG)2(NO3)3]·H2O (2), were synthesized and characterized by elemental analysis, IR, ESI-MS, 1H and 13C NMR as well as single-crystal X-ray diffraction analysis. In vitro the complexes exhibited higher anticancer activity than the free ligand OG against the tested cancer cell lines. Among the tested cell lines, HepG2 is the most sensitive to the complexes. Complex 2 can trigger DNA damage in HepG2 cells, resulting in cell cycle arrest in the S phase and leading to cell apoptosis. The S phase cell-cycle arrest is caused via the ATM (ataxia-telangiectasia mutated)-Chk2-Cdc25A pathway. Chk2 is phosphorylated and activated in an ATM-dependent manner. It, in turn, phosphorylates Cdc25A phosphatise on serine124, causing the inactivation of Cdc25A in ubiquitin-mediated proteolytic degradation. The cyclin-Cdk complexes of the S phase could also be inhibited by limited supply of cyclins A and E. This irreversible cell cycle arrest process ultimately induces mitochondria-involved apoptotic cell death via the activation of Bcl-2 protein. Complex 2 effectively inhibited tumour growth in the BEL-7402 xenograft mouse model and exhibited higher safety in vivo than cisplatin.

We have developed a highly sensitive and selective fluorescence polarization assay method based on the specificity of the DNA cleavage reaction with the enhancement of gold nanoparticles (AuNPs) for assaying endonuclease activity and inhibition. This assay can detect EcoRI endonuclease down to 5.0 × 10−4 U mL−1 with a detection range from 5.0 × 10−4 to 10 U mL−1.

We have developed an amplified chemiluminescence turn-on sensing platform that relies on single-walled carbon nanotubes for ultrasensitive DNA detection. This new type of assay exhibits higher detection sensitivity over traditional biosensors by three orders of magnitude and high specificity for the target molecules.

We have developed an amplified fluorescence polarization aptasensor that relies on aptamer structure-switching-triggered nanoparticles (NPs) enhancement for biomolecules detection. This new type of assay exhibits higher detection sensitivity over traditional homogeneous aptasensors by two orders of magnitude and high specificity for target molecules.