Bioresponsive Mesoporous Silica Nanoparticles for Triggered Drug Release

Mesoporous silica nanoparticles (MSNPs) have garnered a great deal of attention as potential carriers for therapeutic payloads. However, achieving triggered drug release from MSNPs in vivo has been challenging. Here, we describe the synthesis of stimulus-responsive polymer-coated MSNPs and the loading of therapeutics into both the core and shell domains. We characterize MSNP drug-eluting properties in vitro and demonstrate that the polymer-coated MSNPs release doxorubicin in response to proteases present at a tumor site in vivo, resulting in cellular apoptosis. These results demonstrate the utility of polymer-coated nanoparticles in specifically delivering an antitumor payload.National Science Foundation (U.S.) (grant R01-CA124427)National Science Foundation (U.S.) (grant U54-CA119349)National Science Foundation (U.S.) (grant U54-CA119335

Shadows of the colonial past – diverging plant use in Northern Peru and Southern Ecuador

This paper examines the traditional use of medicinal plants in Northern Peru and Southern Ecuador, with special focus on the Departments of Piura, Lambayeque, La Libertad, Cajamarca, and San Martin, and in Loja province, with special focus on the development since the early colonial period. Northern Peru represents the locus of the old Central Andean "Health Axis." The roots of traditional healing practices in this region go as far back as the Cupisnique culture early in the first millennium BC

Traditional medicinal plant use in Northern Peru: tracking two thousand years of healing culture

This paper examines the traditional use of medicinal plants in Northern Peru, with special focus on the Departments of Piura, Lambayeque, La Libertad, Cajamarca, and San Martin. Northern Peru represents the center of the old Central Andean "Health Axis," stretching from Ecuador to Bolivia. The roots of traditional healing practices in this region go at least as far back as the Moche period (AC 100–800). Although about 50% of the plants in use reported in the colonial period have disappeared from the popular pharmacopoeia, the plant knowledge of the population is much more extensive than in other parts of the Andean region. 510 plant species used for medicinal purposes were collected, identified and their vernacular names, traditional uses and applications recorded. The families best represented were Asteraceae with 69 species, Fabaceae (35), Lamiaceae (25), and Solanaceae (21). Euphorbiaceae had twelve species, and Apiaceae and Poaceae 11 species. The highest number of species was used for the treatment of "magical/ritual" ailments (207 species), followed by respiratory disorders (95), problems of the urinary tract (85), infections of female organs (66), liver ailments (61), inflammations (59), stomach problems (51) and rheumatism (45). Most of the plants used (83%) were native to Peru. Fresh plants, often collected wild, were used in two thirds of all cases, and the most common applications included the ingestion of herb decoctions or the application of plant material as poultices

Photoswitching Using Visible Light: A New Class of Organic Photochromic Molecules

A versatile new class of organic photochromic molecules that offers an unprecedented combination of physical properties including tunable photoswitching using visible light, excellent fatigue resistance, and large polarity changes is described. These unique features offer significant opportunities in diverse fields ranging from biosensors to targeted delivery systems while also allowing non-experts ready synthetic access to these materials

Synthesis of carboxylated derivatives of poly(isobutylene-co-isoprene) by azide–alkyne “click” chemistry

The final publication is available at Springer via https://dx.doi.org/10.1038/s41428-018-0130-yThe synthesis of carboxylated derivatives of poly(isobutylene-co-isoprene) (isobutylene–isoprene rubber, IIR) with substitution levels ranging from 1 to 4 mol% and different spacer lengths was accomplished through azide–alkyne Huisgen cycloaddition. Azido-functionalized IIR was first prepared by reacting brominated IIR with sodium azide to full conversion in a 90:10 tetrahydrofuran/N,N-dimethylacetamide mixture. The click reaction of azido-functionalized IIR with acetylenic acids, which was carried out using the copper(I) bromide/N,N,N′,N″,N″-pentamethyldiethylenetriamine catalyst system in tetrahydrofuran, yielded carboxylated IIRs. The products were characterized by 1H NMR and FT-IR spectroscopy, and their molecular weight was determined by size exclusion chromatography analysis. The conversion to carboxylated groups reached up to 100% as determined by NMR spectroscopy but was highly dependent on the type of solvent and the amounts of catalysts and reactants used in the procedures.ARLANXEO Canada Inc.Natural Sciences and Engineering Research Council (NSERC) of Canad

Polymeric dibromomaleimides as extremely efficient disulfide bridging bioconjugation and pegylation agents

A series of dibromomaleimides have been shown to be very efficacious at insertion into peptidic disulfide bonds. This conjugation proceeds with a stoichiometric balance of reagents in buffered solutions in less than 15 min to give discrete products while maintaining the disulfide bridge and thus peptide conformation. The insertion is initiated by disulfide reduction using a water-soluble phosphine, tris(2-carboxyethyl)phosphine (TCEP) which allows for subsequent substitution of the two maleimide bromides by the generated thiols. Reaction of salmon calcitonin (sCT) with 2,3-dibromomaleimide (1.1 excess) in the presence of TCEP (1.1 equiv) in aqueous solution at pH 6.2 gives complete production of a single conjugate which requires no workup. A linear methoxy poly(ethylene glycol) (PEG) was functionalized via a Mitsunobu reaction and used for the successful site-specific and rapid pegylation of sCT. This reaction occurs in 15 min with a small stoichiometry excess of the pegylating agent to give insertion at the disulfide with HPLC showing a single product and MALDI-ToF confirming conjugation. Attempts to use the group in a functional ATRP polymerization initiator led to polymerization inhibition. Thus, in order to prepare a range of functional polymers an indirect route was chosen via both azide and aniline functional initiators which were converted to 2,3-dibromomaleimides via appropriate reactions. For example, the azide functional polymer was reacted via a Huisgen CuAAC click reaction to an alkyne functional 2,3-dibromomaleimide. This new reagent allowed for the synthesis of conjugates of sCT with comb polymers derived from PEG methacrylic monomers which in addition gave appropriate cloud points. This reaction represents a highly efficient polymer conjugation method which circumvents problems of purification which normally arise from having to use large excesses of the conjugate. In addition, the tertiary structure of the peptide is efficiently maintained