Dual-peptide functionalized nanoparticles for therapeutic use

Peptide-functionalized nanoparticles combine the best of both; the ability of nanoparticles to deliver a drug “cargo” throughout the body and the ability of peptides to selectively target certain cell types or biological systems. The vast majority of peptide-functionalized nanoparticles employ only one type of peptide, however, to truly realize the potential of these systems in medicine, nanoparticles equipped with two or even more peptide functionalities are desirable. In this review, the latest developments in dual-peptide functionalized nanoparticles are discussed. These are categorized depending on their structure; first broadly into grafted and self-assembled dual-peptide-nanoparticles with the former then subdivided further into nonconjugated, linearly conjugated and branched conjugated dual-peptide functionalized nanoparticles. These different categories of dual-peptide nanoparticles are then discussed with regards to the type of functional peptides used and their role in selective targeting nanomedicine

Double tailed scorpiand-type calix[10]phyrin: Synthesis and proton-driven anion recognition features

Reported here is a large oligopyrrole macrocycle, a calix[10]phyrin bearing two diformyl substituents. The combination of conjugation provided by two pentapyrrolic subunits and flexibility resulting from the presence of sp3 hybridized meso bridges allows the system to adopt a double tailed, scorpiand-like structure with two near-symmetric binding pockets. In methanol solution, this macrocycle was found to interact with a number of test acids, including sulfuric acid, trifluoroacetic acid, phosphoric acid, hydrochloric acid, and fluoroboric acid, via a combination of protonation and counter anion binding. Species specific behavior was seen, allowing for the colorimetric-based discrimination between the acids. Efforts to model the underlying binding equilibria led to the conclusion that upon treatment with excess H2SO4, up to four protons and two counteranions are bound, whereas in the case of HCl the dominant species is a monoanionic complex. The responses of several other acids were rationalized in terms of these limiting scenarios

Rootless tephra stratigraphy and emplacement processes

Volcanic rootless cones are the products of thermohydraulic explosions involving rapid heat transfer from active lava (fuel) to external sources of water (coolant). Rootless eruptions are attributed to molten fuel–coolant interactions (MFCIs), but previous studies have not performed systematic investigations of rootless tephrostratigraphy and grain-size distributions to establish a baseline for evaluating relationships between environmental factors, MFCI efficiency, fragmentation, and patterns of tephra dispersal. This study examines a 13.55-m-thick vertical section through an archetypal rootless tephra sequence, which includes a rhythmic succession of 28 bed pairs. Each bed pair is interpreted to be the result of a discrete explosion cycle, with fine-grained basal material emplaced dominantly as tephra fall during an energetic opening phase, followed by the deposition of coarser-grained material mainly as ballistic ejecta during a weaker coda phase. Nine additional layers are interleaved throughout the stratigraphy and are interpreted to be dilute pyroclastic density current (PDC) deposits. Overall, the stratigraphy divides into four units: unit 1 contains the largest number of sediment-rich PDC deposits, units 2 and 3 are dominated by a rhythmic succession of bed pairs, and unit 4 includes welded layers. This pattern is consistent with a general decrease in MFCI efficiency due to the depletion of locally available coolant (i.e., groundwater or wet sediments). Changing conduit/vent geometries, mixing conditions, coolant and melt temperatures, and/or coolant impurities may also have affected MFCI efficiency, but the rhythmic nature of the bed pairs implies a periodic explosion process, which can be explained by temporary increases in the water-to-lava mass ratio during cycles of groundwater recharge.We acknowledge financial support from the National Science Foundation (NSF) grant EAR-119648, National Aeronautics and Space Administration (NASA) Mars Data Analysis Program (MDAP) grant NNG05GQ39G, NASA Mars Fundamental Research Program (MFRP) grant NNG05GM08G, NASA Postdoctoral Program (NPP), Geological Society of America (GSA), and Icelandic Centre for Research (RANNÍS). We are grateful to Stephen Scheidt for his help developing photogrammetric reconstructions of Cone 53 and we thank Richard Brown for his editorial handing of this manuscript as well as Peter Reynolds and Adrian Pittari for their constructive reviews.Peer Reviewe

Hydrogels with intrinsic antibacterial activity prepared from naphthyl anthranilamide (NaA) capped peptide mimics

In this study, we prepared antibacterial hydrogels through the self-assembly of naphthyl anthranilamide (NaA) capped amino acid based cationic peptide mimics. These ultra-short cationic peptide mimics were rationally designed with NaA as a capping group, l-phenylalanine, a short aliphatic linker, and a cationic group. The synthesized peptide mimics efficiently formed hydrogels with minimum gel concentrations between 0.1 and 0.3%w/v. The resulting hydrogels exhibited desirable viscoelastic properties which can be tuned by varying the cationic group, electronegative substituent, or counter anion. Importantly, nanofibers from the NaA-capped cationic hydrogels were found to be the source of hydrogels’ potent bacteriacidal actvity against both Gram-positive and Gram-negative bacteria while remaining non-cytotoxic. These intrinsically antibacterial hydrogels are ideal candidates for further development in applications where bacterial contamination is problematic

Landscape evolution associated with the 2014–2015 Holuhraun eruption in Iceland

The 2014–2015 Holuhraun eruption in Iceland developed between the outlet glacier Dyngjujökull and the Askja central volcano and extruded a bulk lava volume of over 1 km3 onto the floodplain of the Jökulsá á Fjöllum river, making it the largest effusive eruption in Iceland during the past 230 years. Time-series monitoring using a combination of traditional aerial imaging, unmanned aerial systems, and field-based geodetic surveys, established an unprecedented record of the hydrological response of the river system to this lava flow. We observed: (1) the formation of lava-dammed lakes and channels produced during dam-breaching events; (2) percolation of glacial meltwater into the porous and permeable lava, forming an ephemeral hydrothermal system that included hot pools and hot springs that emerged from the lava flow front; and (3) the formation of new seepage channels caused by upwelling of water around the periphery of the lava flow. The observations show that lava flows, like the one produced by the 2014–2015 Holuhraun eruption, can cause significant hydrological changes that continue for several years after the lava is emplaced. Documenting these processes is therefore crucial for our interpretation of volcanic landscapes and processes of lava–water interaction on both Earth and Mars

Effect of polar amino acid incorporation on Fmoc-diphenylalanine-based tetrapeptides.

Peptide hydrogels show great promise as extracellular matrix mimics due to their tuneable, fibrous nature. Through incorporation of polar cationic, polar anionic or polar neutral amino acids into the Fmoc-diphenylalanine motif, we show that electrostatic charge plays a key role in the properties of the subsequent gelators. Specifically, we show that an inverse relationship exists for biocompatibility in the solution state versus the gel state for cationic and anionic peptides. Finally, we use tethered bilayer lipid membrane (tBLM) experiments to suggest a likely mode of cytotoxicity for tetrapeptides which exhibit cytotoxicity in the solution state

Lanthanide-based β-Tricalcium Phosphate Upconversion Nanoparticles as an Effective Theranostic Nonviral Vectors for Image-Guided Gene Therapy

Lanthanide-based beta-tricalcium phosphate (β-TCP) upconversion nanoparticles are exploited as a non-viral vector for imaging guided-gene therapy by virtue of their unique optical properties and multi-modality imaging ability, high transfection efficiency, high biocompatibility, dispersibility, simplicity of synthesis and surface modification. Ytterbium and thulium-doped β-TCP nanoparticles (βTCPYbTm) are synthesized via co-precipitation method, coated with polyethylenimine (PEI) and functionalized with a nuclear-targeting peptide (TAT). Further, in vitro studies revealed that the nanotheranostic carriers are able to transfect cells with the plasmid eGFP at a high efficiency, with approximately 60% of total cells producing the fluorescent green protein. The optimized protocol developed comprises the most efficient βTCPYbTm/PEI configuration, the amount and the order of assembly of βTCPYbTm:PEI, TAT, plasmid DNA and the culturing conditions. With having excellent dispersibility and high chemical affinity toward nucleic acid, calcium ions released from βTCPYbTm:PEI nanoparticles can participate in delivering nucleic acids and other therapeutic molecules, overcoming the nuclear barriers and improving the transfection efficacy. Equally important, the feasibility of the upconversion multifunctional nanovector to serve as an effective contrast agent for imaging modality, capable of converting low-energy light to higher-energy photons via a multi-photons mechanism, endowing greater unique luminescent properties, was successfully demonstrated

Two-Dimensional Molecular Patterning by Surface-Enhanced Zn-Porphyrin Coordination

In this contribution, we show how zinc-5,10,15,20-meso-tetradodecylporphyrins (Zn-TDPs) self-assemble into stable organized arrays on the surface of graphite, thus positioning their metal center at regular distances from each other, creating a molecular pattern, while retaining the possibility to coordinate additional ligands. We also demonstrate that Zn-TDPs coordinated to 3-nitropyridine display a higher tendency to be adsorbed at the surface of highly oriented pyrolytic graphite (HOPG) than noncoordinated ones. In order to investigate the two-dimensional (2D) self-assembly of coordinated Zn-TDPs, solutions with different relative concentrations of 3-nitropyridine and Zn-TDP were prepared and deposited on the surface of HOPG. STM measurements at the liquid-solid interface reveal that the ratio of coordinated Zn-TDPs over noncoordinated Zn-TDPs is higher at the n-tetradecane/HOPG interface than in n-tetradecane solution. This enhanced binding of the axial ligand at the liquid/solid interface is likely related to the fact that physisorbed Zn-TDPs are better binding sites for nitropyridines.