Activating Two-Photon Silica Nanoamplifier-Based CHA and FRET for Accurate Ratiometric Bioimaging of Intracellular MicroRNA.

In situ visualization of microRNA (miRNA) in cancer cells and diseased tissues is essential for advancing our comprehension of the onset and progression of associated diseases. Two-photon (TP) imaging, as an imaging technology with high spatiotemporal resolution, deep tissue penetration, and accurate target quantification, has distinctive advantages over single-photon imaging and has attracted increasing attention. Extensive research has been conducted on two-photon dye-doped silica nanoparticles, which exhibit a large two-photon absorption (TPA) cross-section, high fluorescence quantum yield, and excellent biocompatibility. However, the low abundance of RNA in tumor cells leads to insufficient signal output. Based on functional nucleic acid, a catalyzed hairpin self-assembly (CHA) signal amplification strategy, which has simplicity, robustness, and nonenzymatic characteristics, can achieve the amplification of DNA or RNA signals. Here, a two-photon silica nanoamplifier (TP-SNA) utilizing TP dye-doped silica nanoparticles (SiNPs) and functional nucleic acid was constructed, employing triggering catalyzed hairpin self-assembly and fluorescence resonance energy transfer (FRET) for highly sensitive detection and precise TP imaging of endogenous miRNAs in tumor cells and tissues at varying depths. The TP-SNA demonstrated the capability to detect miR-203 with a detection limit of 33 pM. The maximum two-photon tissue penetration depth of the two-photon nanoamplifier was 210 µm. The two-photon nanoamplifier developed in this study makes full use of the advantages of accurate TP ratiometric bioimaging and the CHA signal amplification strategy, which shows good application value for future transformation into clinical diagnosis.

Structure and antitumor and immunomodulatory activities of a water-soluble polysaccharide from Dimocarpus longan pulp.

A new water-soluble polysaccharide (longan polysaccharide 1 (LP1)) was extracted and successfully purified from Dimocarpus longan pulp via diethylaminoethyl (DEAE)-cellulose anion-exchange and Sephacryl S-300 HR gel chromatography. The chemical structure was determined using Infrared (IR), gas chromatography (GC) and nuclear magnetic resonance (NMR) analysis. The results indicated that the molecular weight of the sample was 1.1 × 10(5) Da. Monosaccharide composition analysis revealed that LP1 was composed of Glc, GalA, Ara and Gal in a molar ratio of 5.39:1.04:0.74:0.21. Structural analysis indicated that LP1 consisted of a backbone of → 4)-α-D-Glcp-(1 → 4)-α-D-GALPA-(1 → 4)-α-D-Glcp-(1 → 4)-ß-D-Glcp-(1 → units with poly saccharide side chains composed of → 2)-ß-D-Fruf-(1 → 2)-L-sorbose-(1 → attached to the O-6 position of the α-D-Glcp residues. In vitro experiments indicated that LP1 had significantly high antitumor activity against SKOV3 and HO8910 tumor cells, with inhibition percentages of 40% and 50%, respectively. In addition, LP1 significantly stimulated the production of the cytokine interferon-γ (IFN-γ), increased the activity of murine macrophages and enhanced B- and T-lymphocyte proliferation. The results of this study demonstrate that LP1 has potential applications as a natural antitumor agent with immunomodulatory activity.

(E)-Methyl 3-(3,4-dihy-droxy-phen-yl)acrylate.

The benzene ring in the title compound, C(10)H(10)O(4), makes an angle of 4.4 (1)° with the C-C-C-O linker. The hy-droxy groups are involved in both intra- and inter-molecular O-H⋯O hydrogen bonds. The crystal packing is stabilized by O-H⋯O hydrogen-bonding inter-actions. The mol-ecules of the caffeic acid ester form a dimeric structure in a head-to-head manner along the a axis through O-H⋯O hydrogen bonds. The dimers inter-act with one another through O-H⋯O hydrogen bonds, forming supermolecular chains. These chains are further extended through C-H⋯O hydrogen bonds as well as van der Waals inter-actions into the final three-dimensional architecture.

Functionalised molybdenum disulfide nanosheets for co-delivery of doxorubicin and siRNA for combined chemo/gene/photothermal therapy on multidrug-resistant cancer.

OBJECTIVE: Molybdenum disulfide (MoS2) has been developed for medical uses due to its excellent medically beneficial characteristics. This research was designed to develop a multifunctional nano-drug delivery system based on the nano-structure of MoS2 for combined chemo/gene/photothermal therapy targeting multidrug-resistant cancer. METHODS: MoS2 nanosheets were prepared by a hydrothermal reaction and modified. Afterward, the nanocarrier was characterised. In vitro cytotoxicity of the drug delivery systems on human breast adenocarcinoma cell lines was assessed. KEY FINDINGS: The nanocarrier was a flake-like structure with a uniform hydrodynamic diameter and possessing good colloidal stability. The nanocarrier showed the capacity to be deployed for co-delivery of Doxorubicin (DOX) and siRNA. The release of DOX could be triggered and enhanced by pH and application of near-infrared (NIR) laser. The nanocarrier had a good photothermic response and stability. The nanocarrier had little effect on the cells and exhibited good biocompatibility. Measurement of the therapeutic efficacy showed that synergistic therapy combining chemo-, gene- and photothermal therapy deploying this drug delivery system will achieve a better anticancer effect on drug-resistant cancer cells than DOX alone. CONCLUSIONS: Our results suggest that this drug delivery system has potential application in the therapeutic strategy for drug-resistant cancer.

Functionalized Graphene Oxide as Drug Delivery Systems for Platinum Anticancer Drugs.

Graphene Oxide, prepared by the modified Hummer's method, was modified with a series of high polymers (polyethyleneimine, polyethylene glycol, chitosan) and Folic Acid for the delivery of platinum anticancer drugs including Cisplatin, Carboplatin, Oxaliplatin and Eptaplatin. Nanocarriers were successfully prepared and characterized by Fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscope. Measurement of drug loading efficiency showed that these nanocarriers had the ability for effective delivery of the platinum anticancer drugs. The Maximum loading ratios of Cisplatin, Carboplatin, Oxaliplatin and Eptaplatin were 25.72, 161.08, 345.21 and 67.80 µg/mg. Drug release experiments in the acid environment showed that the cumulative release rate of platinum anticancer drugs from nanocarriers was higher than that in the neutral environment. The cumulative release of all three nanocarriers in the acid environment reached above 60%. In vitro cytotoxicity assay showed that those nanocarriers had a low toxicity. The cell viability rates were above 80% for all three nanocarriers. Investigation of the anticancer activity in vitro showed that those drug delivery systems had the ability to inhibit the growth of the SKOV3 cell line. These results showed that those nanocarriers were suitable for the delivery of platinum anticancer drugs. Providing preliminary advice on the potential application of the combination of platinum anticancer drugs and the functionalized Graphene Oxide nanocarriers.

A potentially valuable nano graphene oxide/USPIO tumor diagnosis and treatment system.

Due to increased requirements for precision cancer treatment, cancer chemotherapy and combination therapies have gradually developed in the direction of diagnosis and treatment integration. In this study, a non-toxic nano carrier that demonstrates integrated MRI signal enhancing performance, as well as better chemotherapy and photothermal conversion performance, was prepared and characterized. Furthermore, the carrier was used to construct an integrated system of tumor diagnosis and treatment. Our in vitro studies showed that this system has a considerable inhibition effect on tumor cells during the treatment of chemotherapy when combined with PTT, and in vivo studies showed that the system could improve the MRI signal of the tumor site with application of a safe dosage. Thus, this system based on NGO/USPIO has the potential to be a multi-functional nano drug delivery system integrating diagnosis and treatment benefits and applications that are worthy of further research.

Preparation and anti-cancer activity of transferrin/folic acid double-targeted graphene oxide drug delivery system.

In this study, a transferrin/folic acid double-targeting graphene oxide drug delivery system loaded with doxorubicin was designed. Graphene oxide was prepared by ultrasound improved Hummers method and was modified with Pluronic F68, folic acid, and transferrin to decrease its toxicity and to allow dual-targeting. The results show that the double target drug delivery system (TFGP*DOX) has good and controllable drug delivery performance with no toxicity. Moreover, TFGP*DOX has a better inhibitory effect on SMMC-7721 cells than does a single target drug delivery system (FGP*DOX). The results of drug release analysis and cell inhibition studies showed that TFGP*DOX has a good sustained release function that can reduce the drug release rate in blood circulation over time and improve the local drug concentration in or near a targeted tumor. Therefore, the drug loading system (TFGP*DOX) has potential application value in the treatment of hepatocellular carcinoma.

Ethyl 3-amino-1-phenyl-1H-benzo[f]chromene-2-carboxyl-ate.

The pyranyl ring of the title compound, C(22)H(19)NO(3), adopts a flattened-boat conformation. The dihedral angle between naphthalene and phenyl rings is 78.3 (1)°The mol-ecule also features an intra-molecular N-H⋯O(carbon-yl) hydrogen bond. Adjacent mol-ecules are linked by an inter-molecular N-H⋯O(carbon-yl) hydrogen bond, forming a zigzag chain that runs along the c axis.

Synthesis of a novel p-hydroxycinnamic amide with anticancer capability and its interaction with human serum albumin.

In the present study, a novel p-hydroxycinnamic amide (E)-3-(4-hydroxyphenyl)-N-(4-(N-(5-meth oxypyrimidin-2-yl)-sulfamoyl)phenyl)acrylamide (HMSP) was synthesized and confirmed. In vitro cytotoxic assays indicated that HMSP was able to inhibit the proliferation of various cancer cell lines. The interaction between HMSP and human serum albumin (HSA) was examined by fluorescence, UV-Vis and circular dichroism (CD) spectra, in addition to molecular simulation. The fluorescence and UV-Vis spectra data indicated that the binding of HMSP with HSA was a static process. According to the fluorescence quenching calculation, the corresponding thermodynamic parameters, bimolecular quenching rate constant and apparent quenching constants were calculated. Van der Walls forces and hydrogen bonds were vital in the binding of HMSP on HSA. The distances between HSA and its derivatives were obtained. Furthermore, competitive experiments and molecular modeling results suggested that the binding of the compound on HSA mainly occurred in site I (sub-domain IIA). Changes in HSA conformation were observed from synchronous fluorescence and CD spectra, which were further investigated by molecular dynamic simulations.

Magnetic Graphene Oxide-Fe3O4-PANI Nanoparticle Adsorbed Platinum Drugs as Drug Delivery Systems for Cancer Therapy.

Graphene-based magnetic nanoparticles (NPs) were synthesized using a simple and effective chemical precipitation method. To determine the biocompatibility of GO-Fe3O4-PANI NPs with MTT assay, cytotoxicity testing from a low concentration (1 µg/mL) to a high concentration (125 µg/mL) was conducted using various cancer and normal cell lines. Cytotoxicity testing for cancer cell lines (SMMC-7721, HepG-2, RAW264.7) and normal cell lines (HL-7702) showed almost no toxicity within the 1~125 µg/mL concentration range. Carboplatin (CBP) and oxaliplatin (OXP) were then used as drug models to study the drug release of CBP and OXP loaded on GO-Fe3O4-PANI NPs in vitro. Results indicated that the release of CBP and OXP from GO-Fe3O4-PANI NPs were affected by pH, dose, and temperature. The release of CBP was more sensitive to pH, and the amounts released in neutral and acidic environments (pH 6.0 and 7.4, respectively) were higher than those released in alkaline environments (pH 8.0). Meanwhile, at different pH levels, the release of OXP was not as large. In addition, at a low temperature (27 °C), the amount released is small when the energy level does not meet that required by C═N. At a considerably higher temperature (47 °C), the energy required for C═N fracture is met, allowing the slow release of the drug over a longer period. The results of our studies suggest that GO-Fe3O4-PANI NPs are biocompatible with MTT assay, and as drug delivery systems, these particular NPs can lead to advances in cancer treatment.

Diacetatobis[1,3-bis-(benzimidazol-2-yl)benzene]zinc(II) dihydrate.

In the title complex, [Zn(CH(3)COO)(2)(C(20)H(14)N(4))(2)]·2H(2)O, the Zn(II) atom, which lies on a crystallographic twofold axis, is coordinated by two O atoms of two acetate ligands and two N atoms from two 1,3-bis-(benzimidazol-2-yl)benzene ligands in a distorted tetra-hedral geometry. The complex mol-ecules and solvent water mol-ecules are connected via O-H⋯N, O-H⋯O and N-H⋯O hydrogen bonds, forming a three-dimensional network.

Functionalized Graphene Oxide as a nanocarrier of new Copper (II) complexes for targeted therapy on nasopharyngeal carcinoma.

Cancer cell targeted therapy using a biocompatible targeted drug delivery system can increase the therapeutic effects of cellular cancer therapy. Here, we report a Folic Acid (FA) and polyethyleneimine (PEI) functionalized Graphene Oxide (GO) nanocarrier, FA-PEI-GO, used to deliver two new Copper complexes into the folate-receptor-positive nasopharyngeal carcinoma cell line. GO was prepared by modified Hummers method and then decorated by PEI and FA. Afterwards, the material was characterized by the X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and atomic force microscopy (AFM). Copper complexes were synthesized by a hydrothermal method and then characterized by single crystal X-ray diffraction analysis. Cytotoxicity assessment of the complexes illustrated that the IC50 values against the nasopharyngeal carcinoma cell lines, HNE-1 and CNE-2, were, respectively, 17.7 ±â€¯1.2, 13.2 ±â€¯1.9, 6.7 ±â€¯0.8, 2.9 ±â€¯0.7 µM. Flow cytometry findings suggested that both complexes were capable of decreasing cancer cell viability through causing late-stage cell apoptosis. The obtained targeted drug delivery systems had good biocompatibility and stability. Compared with Cis-Dichlorodiamineplatinum (CDDP), the non-specific antitumor drug normally used in chemotherapy, one of the obtained agents had similar therapeutic effect while the other had significantly higher activity, suggesting future possible application of this new targeted therapy against nasopharyngeal carcinoma.

Graphene-Based Materials for the Fast Removal of Cytokines from Blood Plasma.

There is a range of medical conditions, which include acute organ failure, bacterial and viral infection, and sepsis, that result in overactivation of the inflammatory response of the organism and release of proinflammatory cytokines into the bloodstream. Fast removal of these cytokines from blood circulation could offer a potentially efficient treatment of such conditions. This study aims at the development and assessment of novel biocompatible graphene-based adsorbents for blood purification from proinflammatory cytokines. These graphene-based materials were chosen on the basis of their surface accessibility for small molecules further facilitated by the interlayer porosity, which is comparable to the size of the cytokine molecules to be adsorbed. Our preliminary results show that graphene nanoplatelets (GnP) exhibit high adsorption capacity, but they cannot be used in direct contact with blood due to the risk of small carbon particle release into the bloodstream. Granulation of GnP using poly(tetrafluoroethylene) as a binder eliminated an undesirable nanoparticle release without affecting the GnP surface accessibility for the cytokine molecules. The efficiency of proinflammatory cytokine removal was shown using a specially designed flow-through system. So far, GnP proved to be among the fastest acting and most efficient sorbents for cytokine removal identified to date, outperforming porous activated carbons and porous polymers.

MXene Sorbents for Removal of Urea from Dialysate: A Step toward the Wearable Artificial Kidney.

The wearable artificial kidney can deliver continuous ambulatory dialysis for more than 3 million patients with end-stage renal disease. However, the efficient removal of urea is a key challenge in miniaturizing the device and making it light and small enough for practical use. Here, we show that two-dimensional titanium carbide (MXene) with the composition of Ti3C2T x, where T x represents surface termination groups such as -OH, -O-, and -F, can adsorb urea, reaching 99% removal efficiency from aqueous solution and 94% from dialysate at the initial urea concentration of 30 mg/dL, with the maximum urea adsorption capacity of 10.4 mg/g at room temperature. When tested at 37 °C, we achieved a 2-fold increase in urea removal efficiency from dialysate, with the maximum urea adsorption capacity of 21.7 mg/g. Ti3C2T x showed good hemocompatibility; it did not induce cell apoptosis or reduce the metabolizing cell fraction, indicating no impact on cell viability at concentrations of up to 200 µg/mL. The biocompatibility of Ti3C2T x and its selectivity for urea adsorption from dialysate open a new opportunity in designing a miniaturized dialysate regeneration system for a wearable artificial kidney.

Sulfated modification of longan polysaccharide and its immunomodulatory and antitumor activity in vitro.

A water-soluble polysaccharide fraction (LP1) was prepared from Dimocarpus longan Lour. by hot water extraction, DEAE-cellulose and Sephadex G-100 chromatography. Its sulfated derivative (LP1-S) was prepared by the sulfuric acid method. Preliminary tests in vitro showed LP1 and LP1-S could stimulate murine lymphocytes proliferation, increase pinocytic activity of murine macrophages and production of nitric oxide (NO), interleukin 6 (IL-6), IL-1ß and tumor necrosis factor-alpha (TNF-α) in macrophages. Furthermore, LP1-S exhibited higher antiproliferative activity against human nasopharyngeal carcinoma HONE1 cells in vitro than LP1, which might be caused by the sulfate group in its structures. These results indicated that the LP1-S might be useful for developing safe antitumor drugs or health food.

The honeycomb network structure of poly[[[mu(2)-1,3-bis(1H-benzimidazol-2-yl)benzene-kappa(2)N(3):N(3')](mu(2)-terephthalato-kappa(2)O:O')zinc(II)] ethanol solvate].

The terephthalate dianion and the bis(imidazolyl)benzene ligand of the title compound, {[Zn(C(8)H(4)O(4))(C(20)H(14)N(4))].C(2)H(6)O}(n), each bridges two adjacent zinc centers, resulting in a layer-type coordination polymer; the zinc center shows tetrahedral coordination. The disordered ethanol solvent molecules occupy the spaces between the layers and are hydrogen bonded to the layers. The two symmetry-independent dianions lie on different inversion sites.

Catena-poly[[aqua(2,2'-bipyridine-kappa2N,N')cadmium(II)]-mu-4-carboxylatophenoxyacetato-kappa3O:O4,O4'].

In the title compound, [Cd(C9H6O5)(C10H8N2)(H2O)]n, the CdII atom is coordinated in a distorted octahedral fashion by two carboxylate groups (one in a monodentate and one in a bidentate fashion) from two 4-carboxylatophenoxyacetate anions, two N atoms from a 2,2'-bipyridine ligand and one aqua ligand. The structure is a helix with a long pitch of 16.441 (5) A. A three-dimensional supramolecular network is further constructed through pi-pi stacking and hydrogen-bonding interactions between the helices.