Delivery of Mir-196c-3p with NIR-II light-triggered gel attenuates cardiomyocyte ferroptosis in cardiac ischemia-reperfusion injury.

Ferroptosis plays an important role in ischemia-reperfusion (I/R)-induced cardiac injury and there are many defects in current targeted delivery of miRNAs for the treatment of ferroptosis. We herein report a unique hydrogel (Gel) that can be triggered by a near-infrared-II (NIR-II) light with deep tissue penetration and biocompatible maximum permissible exposure (MPE) value for in situ treatment after I/R. The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Using 1064 nm light irradiation, local microenvironment photothermal-triggered on-demand noninvasive controllable delivery of miRNA was achieved, aiming to inhibit I/R-induced ferroptosis. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in I/R model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and LOX expression.

Hyaluronic Acid Nanoparticles Based on a Conjugated Oligomer Photosensitizer: Target-Specific Two-Photon Imaging, Redox-Sensitive Drug Delivery, and Synergistic Chemo-Photodynamic Therapy.

Self-assembled hyaluronic acid (HA) nanoparticles have been extensively investigated as anticancer therapeutic agents due to the biocompatibility, biodegradability, and active targeting characteristics of HA. However, many HA nanoparticles are restricted to the applications in drug delivery for chemotherapy or lack effective imaging agents. Hence, we developed the camptothecin (CPT)-loaded HA-SS-BFVPBT nanoparticles (HSBNPs) as a multifunctional platform for two-photon imaging and synergistic chemo-photodynamic therapy at the same time. A novel conjugated oligomer photosensitizer, BFVPBT, which was conjugated onto HA through the redox-responsive disulfide linkage (SS), could not only provide a hydrophobic domain for the formation of nanoparticles and drug entrapment but also act as a two-photon photosensitizer that can be directly excited and simultaneously used in two-photon imaging and photodynamic therapy (PDT). HeLa cells overexpressing the HA receptor (CD44) were used for in vitro studies, which proved the specific cellular uptake of CPT-loaded HSBNPs and excellent two-photon PDT/chemotherapy synergistic effect. The nanoparticles have also been shown to realize tumor-targeting in vivo imaging in HeLa-tumor-bearing mice. Moreover, the fluorescence of CPT-loaded HSBNPs could be activated due to the degradation by the reductive glutathione (GSH) and overexpressed hyaluronidases (Hyal-1) in cancer cells, and the intracellular drug release rate was quickened, thus improving the probability of precise cancer diagnosis and therapy. Accordingly, this HSBNPs system is also anticipated to be a precise nanocarrier for other imaging and therapeutic agents besides CPT, offering a promising new avenue for imaging-guided efficient cancer therapy.

Effective tracking of bone mesenchymal stem cells in vivo by magnetic resonance imaging using melanin-based gadolinium3+ nanoparticles.

Tracking transplanted stem cells is necessary to clarify cellular properties and improve transplantation success. In this study, we designed and synthesized melanin-based gadolinium3+ (Gd3+ )-chelate nanoparticles (MNP-Gd3+ ) of ∼7 nm for stem cell tracking in vivo. MNP-Gd3+ possesses many beneficial properties, such as its high stability and sensitivity, shorter T1 relaxation time, higher cell labeling efficiency, and lower cytotoxicity compared with commercial imaging agents. We found that the T1 relaxivity (r1 ) of MNP-Gd3+ was significantly higher than that of Gd-DTPA; the nanoparticles were taken up by bone mesenchymal stem cells (BMSCs) via endocytosis and were broadly distributed in the cytoplasm. Based on an in vitro MTT assay, no cytotoxicity of labeled stem cells was observed for MNP-Gd3+ concentrations of less than 800 µg/mL. Furthermore, we tracked MNP-Gd3+ -labeled BMSCs in vivo using 3.0T MRI equipment. After intramuscular injection, MNP-Gd3+ -labeled BMSCs were detected, even after four weeks, by 3T MRI. We concluded that MNP-Gd3+ nanoparticles at appropriate concentrations can be used to effectively monitor and track BMSCs in vivo. MNP-Gd3+ nanoparticles have potential as a new positive MRI contrast agent in clinical applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 131-137, 2017.

A Folate-Conjugated Dual-Modal Fluorescent Magnetic Resonance Imaging Contrast Agent that Targets Activated Macrophages In Vitro and In Vivo.

Mucin-1 (MUC1), a transmembrane glycoprotein is aberrantly expressed on ∼90% of breast cancer and is an excellent target for nanoparticulate targeted imaging. In this study, the development of a dye-doped NIR emitting mesoporous silica nanoparticles platform conjugated to tumor-specific MUC1 antibody (ab-tMUC1-NIR-MSN) for in vivo optical detection of breast adenocarcinoma tissue is reported. The structural properties, the in vitro and in vivo performance of this nanoparticle-based probe were evaluated. In vitro studies showed that the MSN-based optical imaging nanoprobe is non-cytotoxic and targets efficiently mammary cancer cells overexpressing human tMUC1 protein. In vivo experiments with female C57BL/6 mice indicated that this platform accumulates mainly in the liver and did not induce short-term toxicity. In addition, we demonstrated that the ab-tMUC1-NIR-MSN nanoprobe specifically detects mammary gland tumors overexpressing human tMUC1 in a human MUC1 transgenic mouse model.

Preparation of MoS2-polyvinylpyrrolidone nanocomposites for flexible nonvolatile rewritable memory devices with reduced graphene oxide electrodes.

A facile method for exfoliation and dispersion of molybdenum disulfide (MoS2) with the aid of polyvinylpyrrolidone (PVP) is proposed. The resultant PVP-coated MoS2 nanosheets, i.e., MoS2-PVP nanocomposites, are well dispersed in the low-boiling ethanol solvent, facilitating their thin film preparation and the device fabrication by solution processing technique. As a proof of concept, a flexible memory diode with the configuration of reduced graphene oxide (rGO)/MoS2-PVP/Al exhibited a typical bistable electrical switching and nonvolatile rewritable memory effect with the function of flash. These experimental results prove that the electrical transition is due to the charge trapping and detrapping behavior of MoS2 in the PVP dielectric material. This study paves a way of employing two-dimensional nanomaterials as both functional materials and conducting electrodes for the future flexible data storage.

Kinetically controlled assembly of a spirocyclic aromatic hydrocarbon into polyhedral micro/nanocrystals.

Nonplane molecules with multiple large aromatic planes could be promising candidates to form various polyhedral micro/nanocrystals by manipulating the different π···π stacking, tuning the cohesive energies of crystal facets, and controlling the kinetic growth process. Spirocyclic aromatic hydrocarbons (SAHs) not only have two cross-shaped aromatic planes but also offer the feature of supramolecular steric hindrance, making it favorable for the heterogeneous kinetic growth into highly symmetric polyhedra. Herein, we report that a novel SAH compound, spiro[fluorene-9,7'-dibenzo[c,h]acridine]-5'-one (SFDBAO), can self-assemble into various monodispersed shapes such as hexahedra, octahedra, and decahedra through the variation of either different types of surfactants, such as Pluronic 123 (P123) and cetyltrimethyl ammonium bromide (CTAB), or growth parameters. In addition, the possible mechanism of crystal facet growth has been proposed according to the SEM, XRD, TEM, and SAED characterization of organic polyhedral micro/nanocrystals. The unique cruciform-shaped SAHs have been demonstrated as fascinating supramolecular synthons for various highly symmetric polyhedral assembling.

The influence of the linkage pattern on the optoelectronic properties of polysilafluorenes: a theoretical study.

Polysilafluorenes have recently received increasing attention for a wide range of optoelectronic applications due to their improved performance over polyfluorenes and polycarbazoles. To reveal their molecular structures, optoelectronic properties, and structure-property relationships, a systematic study of the influence of the linkage pattern on the optoelectronic properties of polysilafluorenes was performed via quantum chemistry calculations. The optimized geometries, electronic properties, frontier molecular orbitals, singlet and triplet energies, ionization potentials, electron affinities, reorganization energies, and absorption and circular dichroism spectra of the model compounds have been calculated and analyzed. The great impacts of the linkage pattern on the structural, electronic, and optical properties of the silafluorene-based materials have been observed, and the effect mode of the linkage pattern has been discussed. Good coordination between the theoretical and experimental results has been found. The unreported poly(1,8-silafluorene)s are expected to be very interesting optoelectronic materials with high electronic bandgap (E(g)) and triplet energy ((3)E(g)), high electron injection property, high hole and electron transport properties, strong circular dichroism signals, and modest effective conjugation length, which can be used as high-performance blue or deep-blue light emitting diodes, ambipolar host materials for blue phosphorescent emitters, and helically chiral conjugated materials.

Macrospirocyclic oligomers based on carbazole and fluorene.

Monodisperse macrospirocyclic oligomers were prepared using self-condensation of the Friedel-Crafts reaction. Through the C-9s of the central fluorene units of four surrounding oligofluorenes, four carbazole units are connected in a series to form a macrocyclic core. These rodlike oligofluorenes form a rigid three-dimensional structure, affording the resulting macrocyclics a high steric hindrance for close interchain packing.

Solvent- and pH-induced self-assembly of cationic meta-linked poly(phenylene ethynylene): effects of helix formation on amplified fluorescence quenching and Förster resonance energy transfer.

We reported here the synthesis and characterization of a novel water-soluble, meta-linked poly(phenylene ethynylene) (m-PPE-NEt(2)Me(+)) featuring quaternized side groups. We studied the solvent-induced self-assembly of m-PPE-NEt(2)Me(+) in MeOH/H(2)O solvent mixtures by using UV-vis absorption and fluorescence spectroscopies. The results showed that the polymer folded into a helical conformation and that the extent of helical folding increased with the volume % water in the solvent. This cationic polymer also exhibited unique pH-induced helix formation, which was attributed to the partial neutralization of quaternized side groups at high pH and the meta-links in the main chain of the polymer. Studies on the fluorescence quenching of m-PPE-NEt(2)Me(+) by anthraquinone-2,6-disulfonate (AQS) and Fe(CN)(6)(4-), two small-molecule anionic quenchers with different typical structures, revealed more efficient quenching of helical conformation by AQS than by Fe(CN)(6)(4-). We proposed that the two quenchers most likely interacted with the polymer helix in two different modes; that was, AQS featuring large planar aromatic ring could intercalate within adjacent π-stacked phenylene ethynylene units in the polymer helix, whereas Fe(CN)(6)(4-) mainly bound to the periphery of polymer helix through ion-pair formation. Finally, the results of FRET from the helical polymer to the fluorescein (C*)-labeled polyanions, ssDNA-C* (ssDNA: single-stranded DNA) and dsDNA-C* (dsDNA: double-stranded DNA) also suggested two different modes of interactions. As compared with the FRET to dsDNA-C*, the FRET to ssDNA-C* was slightly more efficient, which was believed to arise from the additional binding of ssDNA-C* with the polymer via intercalation of its exposed hydrophobic bases into the π stack of adjacent phenylene ethynylene units in the polymer helix.

Effects of Temperature and Solvent on the Energy Transfer and ß-Phase Formation in the Iridium(III) Complex-Containing Polyfluorene in Solutions and as Suspended Nano-Particles.

The effects of temperature and solvent on the ß-phase formation and energy transfer in an Ir(III) complex-containing polyfluorene were investigated. Efficient energy transfer from polyfluorenes host to Ir complexes guest can be realized at low temperature. The formation of ß-phase was observed both in THF solution at low temperature and as suspended nano-particles at room temperature. In addition, phosphorescent polymer nanoparticles were prepared successfully and exhibited efficient phosphorescent emission.

Tuning backbones and side-chains of cationic conjugated polymers for optical signal amplification of fluorescent DNA detection.

Three cationic conjugated polymers (CCPs) exhibiting different backbone geometries and charge densities were used to investigate how their conjugated backbone and side chain properties, together with the transitions of DNA amphiphilic properties, interplay in the CCP/DNA-C* (DNA-C*: fluorophore-labeled DNA) complexes to influence the optical signal amplification of fluorescent DNA detection based on Förster resonance energy transfer (FRET). By examining the FRET efficiencies to dsDNA-C* (dsDNA: double-stranded DNA) and ssDNA-C* (ssDNA: single-stranded DNA) for each CCP, twisted conjugated backbones and higher charge densities were proved to facilitate electrostatic attraction in CCP/dsDNA-C* complexes, and induced improved sensitivity to DNA hybridization. Especially, by using the CCP with twisted conjugated backbone and the highest charge density, a more than 7-fold higher efficiency of FRET to dsDNA-C* was found than to ssDNA-C*, indicating a high signal amplification for discriminating between dsDNA and ssDNA. By contrast, linear conjugated backbones and lower charge density were demonstrated to favor hydrophobic interactions in CCP/ssDNA-C* complexes. These findings provided guidelines for the design of novel sensitive CCP, which can be useful to recognize many other important DNA activities involving transitions of DNA amphiphilic properties like DNA hybridization, such as specific DNA binding with ions, some secondary or tertiary structural changes of DNA, and so forth.

Self-assembly of a novel alternant amphiphilic poly(OPE-alt-TEO) copolymer: from nanowires to twist fibrillar architectures with molecular dimensions.

A novel alternant amphiphilic polymer poly[1,4-bis(phenylethynyl)-2,5-bis(hexyloxy)benzene-alt-tetra(ethylene oxide)] was prepared. Atom force microscope (AFM) images showed that the molecular self-assembly morphologies changed from molecular nanowires to twist fibrillar architectures with the increase of the solution concentrations. Short and thin wires formed in dilute solution, while large bundles developed in relatively concentrated ones, shown by fluorescence microscope images. The photoluminescence (PL) spectra of the corresponding films indicate a self-assembly process of the polymers under slow solvents evaporation. Coplanar aggregation was confirmed through PL and photoluminescence excitation (PLE) spectra. Furthermore, the self-assembly process in polymer bulk was studied by wide-angle X-ray diffraction. To the best of our knowledge, it is the first time to reveal the change of the molecular morphologies with the altering concentration for the alternant amphiphilic conjugated polymers.

Synthesis, structure, and optoelectronic properties of phosphafluorene copolymers.

Copolymers of phosphafluorenes are obtained through Suzuki copolymerization. The phosphorus-containing copolymers show unique optical, electrochemical, and optoelectronic properties. Blue and white electroluminescence can be observed, depending on the modifications of the phosphorus atoms. It is the first time that conjugated polymers containing phosphafluorene have been prepared and used in PLEDs. Phosphafluorenes are new building blocks for conjugated oligomers and polymers.

Supramolecule-regulated photophysics of oligo(p-phenyleneethynylene)-based rod-coil block copolymers: effect of molecular architecture.

Three new topology-varied rod-coil block copolymers, comprising the same oligo(p-phenyleneethynylene) (OPE) rod components and the same coil components, were synthesized by atom-transfer radical polymerization. Their photophysical properties were systematically studied and compared in consideration of their solid-state structures and self-assembly abilities. These copolymers have similar intrinsic photophysical properties to the OPE rods, as reflected in dilute solution. However, their photophysical properties in the solid state are manipulated to be dissimilar by supramolecular organization. Wide-angle X-ray diffraction (WAXD) and atomic force microscopy (AFM) data demonstrate that these copolymers possess different self-assembly abilities due to the molecular-architecture-dependent pi-pi interactions of the rods. Hence, the aggregates in the solid state are formed with a different mechanism for these copolymers, bringing about the discrepancy in the solid-state luminescent properties.

Solvent-free atom transfer radical polymerization for the preparation of poly(poly(ethyleneglycol) monomethacrylate)-grafted Fe3O4 nanoparticles: synthesis, characterization and cellular uptake.

Poly(poly(ethyleneglycol) monomethacrylate) (P(PEGMA))-grafted magnetic nanoparticles (MNPs) were successfully prepared via a solvent-free atom transfer radical polymerization (ATRP) method. The macroinitiators were immobilized on the surface of 6.4+/-0.8 nm Fe(3)O(4) nanoparticles via effective ligand exchange of oleic acid with 3-chloropropionic acid (CPA), which rendered the nanoparticles soluble in the PEGMA monomer. The so-obtained P(PEGMA)-grafted MNPs have a uniform hydrodynamic particle size of 36.0+/-1.2 nm. The successful grafting of P(PEGMA) on the MNP surface was ascertained from FTIR and XPS analyses. The uptake of the MNPs by macrophage cells is reduced by two-orders of magnitude to <2 pg Fe/cell after surface grafting with P(PEGMA). Furthermore, the morphology and viability of the macrophage cells cultured in a medium containing 0.2 mg/mL of P(PEGMA)-grafted MNPs were found similar to those of cells cultured without nanoparticles, indicating an absence of significant cytotoxicity effects. T(2)-weighted magnetic resonance imaging (MRI) of P(PEGMA)-grafted MNPs showed that the magnetic resonance signal is enhanced significantly with increasing nanoparticle concentration in water. The R(1) and R(2) values per millimole Fe, and R(2)/R(1) value of the P(PEGMA)-grafted MNPs were calculated to be 8.8 mm(-1)s(-1), 140 mm(-1)s(-1), and 16, respectively. These results indicate that the P(PEGMA)-grafted MNPs have great potential for application in MRI of specific biotargets.

Structural, electronic, and optical properties of 9-heterofluorenes: a quantum chemical study.

Density-functional theory studies were applied to investigate the structural, electronic, and optical properties of 9-heterofluorenes achieved by substituting the carbon at 9 position of fluorene with silicon, germanium, nitrogen, phosphor, oxygen, sulfur, selenium, or boron. These heterofluorenes and their oligomers up to pentamers are highly aromatic and electrooptically active. The alkyl and aryl substituents of the heteroatom have limited influence, but the oxidation of the atom has significant influence on their molecular structures and properties. The highest occupied molecular orbital (HOMO)-lowest occupied molecular orbital (LUMO) interaction theory was successfully applied to analyze the energy levels and the frontier wave functions of these heterofluorenes. Most heterofluorenes belong to type B of interaction with low-lying LUMO and have the second kind of wave function. Carbazole and selenafluorene have type C of interaction with high-lying HOMO and the third kind of wave function. Types C and D of heterofluorenes, such as carbazole, oxygafluorene, sulfurafluorene, and selenafluorene also have high triplet state energies. The extrapolated HOMO and LUMO for polyheterofluorenes indicate that polyselenonafluorene has the lowest LUMO; polycarbazole has the highest HOMO; polyselenafluorene has the highest bandgap (E(g)); and polyborafluorene has the lowest E(g). Heterofluorenes and their oligomers and polymers are of great experimental interests, especially those having extraordinary properties revealed in this study.

Direct laser desorption/ionization time-of-flight mass spectrometry of conjugated polymers.

Two conjugated polymers (CPs), poly(9,9-dioctylfluorene) (PF) and poly(3-octylthiophene) (PT) were analyzed by direct laser desorption/ionization time-of-flight mass spectrometry (LDI-ToF MS). Because of their strong absorption near the wavelength of the laser (337 nm), easy and transient energy transfer properties and sufficient thermal stability, CPs can be desorbed and ionized directly without a matrix. For comparison, these two polymers were also analyzed using matrix-assisted laser desorption/ionization (MALDI)-ToF MS in the positive reflectron mode. The results revealed that they are very similar in terms of quality and resolution. All results demonstrate that LDI-ToF MS is an alternative method for the mass characterization of some conjugated systems, thereby simplifying the process of sample preparation and result analysis.

A facile route to semiconductor nanocrystal-semiconducting polymer complex using amine-functionalized rod-coil triblock copolymer as multidentate ligand.

A facile strategy affording an intimate nanocomplex of an amine-containing rod-coil triblock copolymer poly(2-(dimethylamino)ethylmethacrylate)-poly(fluorene)-poly(2-(dimethyl amino) ethylmethacrylate) and CdSe nanocrystals is presented. Ligand exchange is observed by (31)P NMR. TEM and UV-vis absorption results indicate the CdSe NCs have a good dispersion in the conjugated polymer. Also, the PL spectra show photoinduced charge transfer has been facilitated by the complex formation.

Theoretical investigation of the tunable behavior of p-n copolymers based on oligothiophenes and 1,4-bis(oxadiazolyl)-benzene.

Semiempirical calculations were carried out on several model oligomers to investigate the tunable behavior of p-n copolymers with the repeating units constructed by oligothiophenes as the pi-excessive type blocks and 1,4-bis(oxadiazolyl) benzene as the pi-deficient type block. The calculated evolutions of the HOMO and LUMO of the model oligomers were in good agreement with the experimental oxidation and reduction potentials of the corresponding polymers. The effect of the length of the oligothiophene on the electronic structures and optical properties was elucidated by analyzing the HOMO and LUMO spatial distribution patterns of the model oligomers. When the number of thiophene rings increases, the HOMO and LUMO are contributed mostly from the oligothiophene segments and either the introduced single positive or negative charge focuses on the oligothiophene segments. The absorption spectra of polymers were also simulated by performing calculations on the corresponding oligomers. Good matches were observed between the calculated absorption spectra and the experimental UV-vis spectra of the corresponding polymers. The study shows that the backbone modification of the p-n copolymer, that is, changing the number of thiophene unit in the p-n diblock copolymer, greatly modifies the optical properties of the polymer.