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LyP-1-fMWNTs enhanced targeted delivery of MBD1siRNA to pancreatic cancer cells.

Functionalized multi-walled carbon nanotubes have been extensively gained popularity in pancreatic cancer gene therapy. LyP-1, a peptide, has been proved to specifically bind pancreatic cancer cells. The potential therapeutic effect of LyP-1-conjugated functionalized multi-walled carbon nanotubes in treating pancreatic cancer is still unknown. In this study, LyP-1-conjugated functionalized multi-walled carbon nanotubes were successfully synthesized, characterized and showed satisfactory size distribution and zeta potential. Compared with functionalized multi-walled carbon nanotubes, cellular uptake of LyP-1-functionalized multi-walled carbon nanotubes was shown to be increased. Compound of LyP-1-functionalized multi-walled carbon nanotubes and MBD1siRNA showed superior gene transfection efficiency. Moreover, LyP-1-fMWNTs/MBD1siRNA complex could significantly decrease the viability and proliferation and promoted apoptosis of pancreatic cancer cells in vitro. Further xenograft assays revealed that the tumour burden in the nude mice injected with LyP-1-functionalized multi-walled carbon nanotubes/MBD1siRNA was significantly relieved. The study demonstrated that LyP-1-functionalized multi-walled carbon nanotubes/MBD1siRNA could be a promising candidate for tumour active targeting therapy in pancreatic cancer.

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Reversible Covalent Assembly of Nanoparticles Through On-Surface Diels-Alder Reaction.

We demonstrate here a controlled assembly of individual nanoscale building blocks into defined architectures based on chemospecific covalent bonding interactions. For this purpose, Fe2O3, -Fe2O3 and SiO2 nanoparticles decorated with surface-conjugated organic ligands were used for performing on surface Diels-Alder reactions. Driven through their chemical affinity and surface-grafted complementary functionalities, nanoparticles underwent click-reactions to produce covalently organized nanostructures. An advantage of using the Diels-Alder reaction is its reversible nature, which was used to click and un-click nanoparticles on demand. The efficiency and chemical specificity of this approach opens up another synthetic access to unify materials with complementary properties, where the thermoresponsive nature of particle assemblies imparts them a fully reversible character. The covalent conjugation strategies demonstrated in this work potentially allow use of a diverse range of particles and ligands for their applications in different disciplines such as medicine, optics or photonics. The nanoparticles morphology and crystalline nature was investigated by TEM and XRD analysis, while the presence of surface attached groups was verified by NMR, FTIR, UV-vis and ζ Potential measurements.

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includes 10 mM dNTP, 10 x Includes 5 X reaction buf PCR Sure Kit HBV surface recombinant a ProPrep™ BAC 960 High-T Reaction Buffer, 2X Hepatitis B surface Ag (H ReadiLink™ mFluor™ Vi ReadiLink™ iFluor™ 70 Beta Amyloid (1 42) ELISA Mouse Anti-HAV Surface Ag T7 RNA Polymerase Include

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In Situ Genetically Cascaded Amplification for Imaging RNA Subcellular Locations.

In situ amplification methods, such as hybridization chain reaction, are valuable tools for mapping the spatial distribution and subcellular location of target analytes. However, the live-cell applications of these methods are still limited due to challenges in the probe delivery, degradation and cytotoxicity. Herein, we report a novel genetically encoded in situ amplification method to non-invasively image the subcellular location of RNA targets in living cells. In our system, a fluorogenic RNA reporter, Broccoli, was split into two non-fluorescent fragments and conjugated to the end of two RNA hairpin strands. The binding of one target RNA can then trigger a cascaded hybridization between these hairpin pairs and thus activate multiple Broccoli fluorescence signal. We have shown that such in situ amplified strategy can be used for the sensitive detection and location imaging of various RNA targets in living bacterial and mammalian cells. This new design principle provides an effective and versatile platform for tracking various intracellular analytes.

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Target Alpha Therapy with Thorium-227.

Targeted alpha therapy (TAT) can deliver high localized burden of radiation selectively to cancer cells as well as the tumor microenvironment, while minimizing toxicity to normal surrounding cell. Radium-223 (Ra), the first-in-class a-emitter approved for bone metastatic castration-resistant prostate cancer has shown the ability to prolong patient survival. Targeted Thorium-227 (Th) conjugates represent a new class of therapeutic radiopharmaceuticals for TAT. They are comprised of the α-emitter Th complexed to a chelator conjugated to a tumor-targeting monoclonal antibody. In this review, the authors will focus out interest on this therapeutic agent. In recent studies Th-labeled radioimmunoconjugates showed a relevant stability both in serum and vivo conditions with a significant antigen-dependent inhibition of cell growth. Unlike Ra, the parent radionuclide Th can form highly stable chelator complexes and is therefore amenable to targeted radioimmunotherapy. The authors discuss the future potential role of Th TAT in the treatment of several solid as well as hematologic malignancies.

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In Situ Light-Initiated Ligands Crosslinking Enables Efficient All-Solution-Processed Perovskite Light-Emitting Diodes.

Solution process has been considered to be an effective method to fabricate emitting layer (EML) in light-emitting diodes (LEDs). However, the fabrication of charge transport layer (CTL) above the perovskite EML by solution processing is challenging. Herein, we incorporated polymerizable molecules, conjugated linoleic acid (CLA), as surface ligands to passivate perovskite QDs. The polymerized CLA can create a crosslinked QD film, which allows the solution deposition of subsequent CTLs. The theoretical calculations reveal that the binding energy of polymerized CLA with QDs increased, and the strong ligands binding state can better passivate the surface and improve the stability of QDs. As a result, all-solution-processed multilayer perovskite LEDs were fabricated with performance of a max luminance of 2470 cd/m2 for CsPbBr3-based devices, and a peak EQE of 2.67% for CsPbI3-based devices. These results demonstrate that the in situ light-initiated ligands crosslinking can be an effective strategy in all-solution-processed optoelectronic devices.

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Cell-Selective Cytotoxicity of a Fluorescent Rhodium Metalloinsertor Conjugate Results from Irreversible DNA Damage at Base Pair Mismatches.

Up to twenty percent of solid tumors are characterized by DNA mismatch repair (MMR) deficiency and microsatellite instability (MSI) that confer resistance to standard of care chemotherapy. MMR-deficient cancers have an increased mutation rate and accumulate DNA mismatches. We previously described a class of compounds, rhodium metalloinsertors, that bind DNA mismatches with high specificity and selectivity and have potential as targeted therapy. [Rh(chrysi)(phen)(PPO)]2+ (RhPPO) is the most potent, selective compound in this class and acts by targeting DNA mismatches, resulting in preferential cytotoxicity to MMR-deficient cancers. To explore further the cellular mechanism of action of RhPPO, we conjugated the metal complex to a fluorescent probe, cyanine 3 (Cy3). RhPPO-Cy3 binds DNA mismatches and retains the selectivity and potent cytotoxic activity of RhPPO for MMR-deficient cell lines. RhPPO-Cy3 forms discrete foci in the cell nucleus that overlap with sites of DNA damage, suggesting that the lesions occur at or near DNA mismatch sites. RhPPO-Cy3 foci persist over time, despite initial processing of the lesion and recruitment of repair proteins, consistent with the idea that the complex binding to a mismatch prevents repair. RhPPO-Cy3 binding does not lead to activation of p53 and the apoptotic pathway. Together, these findings support the idea that RhPPO-Cy3 binding leads to irreversible DNA damage at DNA mismatches that enables selective cytotoxicity to MMR-deficient cells.

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Synthesis and Reactivity of Cationic Boron Complexes Distorted by Pyridine-based Pincer Ligands: Isolation of a Photochemical Hofmann-Martius-type Intermediate.

A family of cationic boron complexes was synthesized, using a dianilidopyridine pincer ligand, which imposes in-plane distortion of the geometry at boron towards T-shaped. Reactivity of these cations toward hydride and base was investigated, and the utility of these cations as precursors to a variety of π-conjugated BN heterocycles was demonstrated. 300 nm irradiation of a deprotonated pincer boron complex triggered a C-N cleavage/C-C formation yielding a dearomatized boryl imine, which has a structure akin to the long-proposed intermediate in the photochemical Hofmann-Martius rearrangement. The photo-rearrangement triggers relief of the distortion imposed by the pincer ligand.

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A novel approach enables imaged capillary isoelectric focusing analysis of PEGylated proteins.

PEGylation has been used as a strategy to enhance pharmacokinetic properties of therapeutic proteins by pharmaceutical industry. Imaged capillary isoelectric focusing (icIEF) is the current industry standard technology for isoelectric point (pI) determination and charge variant quantification of proteins and antibodies. However, the charge variants of PEGylated proteins merge into one broad peak during icIEF, most likely due to masking of proteins by the surrounding polyethylene glycol chain as well as the increased hydrodynamic volume due to PEGylation. Here we report our novel matrix formula with a combination of glycine and taurine (GLY-T) that significantly improved the separation of charge variants in PEGylated proteins. As a result, it is no longer necessary to conduct isoelectric focusing of proteins prior to PEGylation, which does not reflect the changes caused by PEGylation and purification processes. The novel matrix (GLY-T) enables icIEF analysis of PEGylated proteins in their real conjugated states. This article is protected by copyright. All rights reserved.

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Nanoscale Surface-induced Unfolding of Single Fibronectin is Restricted by Serum Albumin Crowding.

Understanding nanoscale protein conformational changes at solid-liquid interfaces is critical for predicting how proteins will impact the performance of biomaterials in vivo. Crowding is an important contributor to conformational stability. Here we apply single-molecule high resolution imaging with photobleaching (SHRImP) to directly measure dye-conjugated fibronectin's unfolding in varying conditions of crowding with human serum albumin on aminosilanized glass. Using this approach, we identify serum albumin's crowding mechanism. We find that fibronectin achieves larger degrees of unfolding when not crowded by co-adsorbed serum albumin. Serum albumin does not as effectively constrict fibronectin's conformation if it is sequentially, rather than simultaneously, introduced, suggesting that serum albumin's crowding mechanism is dependent on its ability to sterically block fibronectin's unfolding during the process of adsorption. Because fibronectin's conformation is dependent on interfacial macromolecular crowding under in vitro conditions, it is important to consider the role of in vivo crowding on protein activity.

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NLO-active Y-shaped ferrocene conjugated imidazole chromophores as precursors for SHG polymeric films.

New Y-shaped ferrocene conjugated imidazole chromophores were prepared and fully characterized. The Y-shaped structure was confirmed by the single crystal X-ray diffraction technique. The chromophores show interesting second-order nonlinear optical (NLO) properties in solution, as determined by the Electric-Field Induced Second Harmonic generation (EFISH) technique. Remarkably, the trifluoro substituted compound 3 is characterized by a high μβEFISH value and has good potential as a molecular building block for composite films with Second Harmonic Generation (SHG) properties. For all compounds, the dipole moments and frontier orbital energies were calculated by the Density Functional Theoretical method.

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