Anticancer Activity of Nano-formulated Orlistat-Dopamine Conjugates Through Self-Assembly.

Orlistat, an FDA-approved fatty acid inhibitor for obesity treatment, demonstrates certain low and greatly varied anticancer abilities. In a previous study, we revealed a synergistic effect between orlistat and dopamine in cancer treatment. Here, orlistat-dopamine conjugates (ODCs) with defined chemical structures were synthesized. The ODC by design underwent polymerization and self-assembly in the presence of oxygen to form nano-sized particles (Nano-ODCs) spontaneously. The resulted Nano-ODCs of partial crystalline structures demonstrated good water dispersion to form stable Nano-ODC suspensions. Because of the bioadhesive property of the catechol moieties, once administered, Nano-ODCs were quickly accumulated on cell surfaces and efficiently uptaken by cancer cells. In the cytoplasm, Nano-ODC experienced biphasic dissolution followed by spontaneous hydrolysis to release intact orlistat and dopamine. Besides elevated levels of intracellular reactive oxygen species (ROS), the co-localized dopamine also induced mitochondrial dysfunctions through monoamine oxidases (MAOs)-catalyzed dopamine oxidation. The strong synergistic effects between orlistat and dopamine determined a good cytotoxicity activity and a unique cell lysis mechanism, explaining the distinguished activity of Nano-ODC to drug-sensitive and -resistant cancer cells. This new technology-enabled orlistat repurposing will contribute to overcoming drug resistance and the improvement of cancer chemotherapy.

Phase separation enabled silver nano-array.

The surface-supported silver nanoparticles have been studied and applied in various applications. Many unique nanostructures have been introduced into this field to improve the functionalities of the surfaces depending on application purposes. We created featured silver nano-array surfaces by utilizing the solvent-mediated phase transition on the surface grafted with poly (acrylic) acids polymer chains and taking advantage of the low temperature of argon gas discharged plasma as a reducing agent. The applied solvents and grafted polymer chain densities affected the phase transition and thus determined the outcome of surface nano-array patterns. However, the total loaded silver ions on the surface affected silver nano-array structures at the sub-micron levels. The featured silver patterned surfaces made in the optimal conditions present a favorable surface-enhanced Raman spectroscopy enhancement as well as recyclability for detection re-usage. This novel method prepares tunable silver nanopatterned surfaces and provides a new approach to various potential applications.

Arthrinium bambusicola (Fungi, Sordariomycetes), a new species from Schizostachyum brachycladum in northern Thailand.

BACKGROUND: Species of the fungal genus Arthrinium (Sordariomycetes, Amphisphaeriales, Apiosporaceae) are often found on bamboo in Asia. They are endophytes, saprobes and important plant pathogens. The genus Arthrinium currently contains 92 species and is widely distributed in North and South America, Europe, Africa, Asia and Oceania. NEW INFORMATION: In this study, a new species, Arthrinium bambusicola sp. nov., is described and illustrated. The new taxon is characterised by oval to broadly or irregularly round, medium brown, multi-guttulate to roughened, granular conidia, with finely pale slits in the outer edges. Arthrinium bambusicola can be distinguished from the closest related species A. gutiae by its conidial characteristics. Phylogenetic analyses of a four-locus dataset (ITS, LSU, TEF1, TUB2) confirm that A. bambusicola is a distinct new species.

Controlled released of drug from doubled-walled PVA hydrogel/PCL microspheres prepared by single needle electrospraying method.

Poly(vinyl alcohol) (PVA) hydrogels have been extensively studied as drug delivery systems. However, due to the high hydrophilicity of PVA, these hydrogels have weak abilities to efficiently load drugs and control the initial burst release. In this study, we present a one-step simple and rapid single needle electrospraying (SNESy) method that combines PVA hydrogels with another biocompatible polymer polycaprolactone (PCL). A distinct core-shell structure was obtained with the PVA hydrogel core and PCL shell after the system was properly set up. The results revealed that the volume ratio between PVA hydrogel and PCL played an important role in determining the particle size and the formation of a spherical structure. The double-walled structure of the microsphere was confirmed by taking the fluorescent images and conducting the ATR-FTIR method. Furthermore, doxorubicin hydrochloride was used as a model drug to evaluate the drug loading capacity and the in vitro release behavior of this PVA hydrogel/PCL microsphere. The results indicated that coating a layer of PCL polymer significantly enhanced the drug loading capacity and reduced the drug initial burst release compared to the single-layer PVA hydrogel nanoparticles, demonstrating these biocompatible double-walled microspheres can be applied as excellent drug delivery carriers.

Oleic acid in the absence of a PPARγ agonist increases adipogenic gene expression in bovine muscle satellite cells1.

We hypothesized that oleic acid (OA) in the absence of a thiazolidinedione (i.e., a synthetic peroxisome proliferator-activated receptorγ [PPARγ] agonist) would increase adipogenic gene expression in bovine muscle satellite cells (BSC). The BSC were cultured in differentiation medium containing 10 µM ciglitazone (CI), 100 µM OA, or 100 µM OA plus 10 µM CI (CI-OA). Control (CON) BSC were cultured only in differentiation media (containing 2% horse serum). The presence of myogenin, desmin, and paired box 7 proteins was confirmed in the BSC by immunofluorescence staining, demonstrating that we had isolated myogenic cells. The OA BSC had lesser paired box 3 (Pax3) and myogenic differentiation 1 expression but greater Pax7 and mygogenin (MYOG) expression (P < 0.05), than the CON BSC. The CI BSC had greater Pax3, Pax7, and MYOG expression than CON BSC (P < 0.05), suggesting that CI would promote BSC myogenesis under pro-myogenic conditions (i.e., when cultured with horse serum). However, both the OA and CI treatments upregulated the expression of PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα) and C/EBPß, sterol regulatory element-binding protein 1, lipoprotein lipase, and glycerol-3-phosphate acyltransferase 3 gene expression, as well as media adiponectin concentration (P < 0.05). The CI, OA, and CI-OA treatments also increased triacylglycerol and lipid droplet accumulation, in spite of upregulation (relative to CON BSC) of adenosine monophosphate-activated protein kinase alpha-1, perilipin 2 (PLIN2), and PLIN3 in BSC and downregulation of G protein-coupled protein receptor 43, acyl-CoA synthetase long chain family member 3, and stearoyl-CoA desaturase (P < 0.05). These results indicate that OA in the absence of a synthetic PPARγ agonist can effectively increase adipogenic gene expression in BSC.

Stereochemical Strategy Advances Microbially Antiadhesive Cotton Textile in Safeguarding Skin Flora.

Microbial contamination on cotton textiles (CT) negatively affects people's health as well as the textile itself during use and storage. Using antimicrobial CT in a body-safe manner is currently still a challenge because it is difficult to balance killing microbes and protecting skin flora. Herein, a borneol-decorated CT (BDCT) through coupling of borneol 4-formylbenzoate molecules onto the amino-modified CT is reported. This BDCT shows strong and broad-spectrum microbially antiadhesive activities against gram-positive bacteria (Staphylococcus aureus and S. epidermidis), gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and fungi (Aspergillus niger, Mucor racemosus, and Candida albicans). Because of its unique stereochemical microbial antiadhesion mechanism, BDCT is harmless to skin flora. In addition, BDCT exhibits prominent durability of microbially antiadhesive capability by bearing 50 times of accelerated laundering. Therefore, this stereochemical BDCT strategy shows great potential for applications in the new generation of textiles, food packaging, and medical protection.

Looking for Lepiotapsalion Huijser & Vellinga (Agaricales, Agaricaceae).

Lepiotapsalion is fully described based on a recent collection from Sardinia (Italy) and the holotype. NrITS- and nrLSU-based phylogeny demonstrates that sequences deposited in GenBank as "L.psalion" and generated from two Dutch and one Chinese collections are not conspecific with the holotype and represent two distinct, undescribed species. These species are here proposed as Lepiotarecondita sp. nov. and Lepiotasinorecondita ad int.

Polydopamine-Decorated Orlistat-Loaded Hollow Capsules with an Enhanced Cytotoxicity against Cancer Cell Lines.

Orlistat, an FDA-approved antiobesity drug, has recently been shown to have anticancer effects. However, orlistat is extremely hydrophobic with low absorption. Therefore, new approaches are needed to effectively deliver orlistat for cancer therapy. Herein, we developed a fast and simple method to use polydopamine-coated hollow capsule (PHC) as a drug nanocarrier for enhancing the therapeutic effects of orlistat. Orlistat-loaded PHC had an average size of 200 nm, which was characterized by using dynamic light scattering and scanning electron microscope. Furthermore, the polydopamine layer provided an excellent control of orlistat release because it was extremely sensitive to pH values. The cellular uptake and cytotoxicity experiments were performed to show that orlistat packaged in PHC could be endocytosed into cells and then significantly improved the cytotoxic activity against cancer cell lines in a short time compared with free orlistat. Moreover, dynamic study of cell membrane lysis was performed by staining with the LIVE/DEAD kit to demonstrate the cancer-killing mechanism. The size of the cell surface area has also been proven to be a key parameter which affected drug efficacy. Taken all together, these results present that orlistat-loaded PHC is a very promising formula for cancer treatments.

The dataset of scanning electron microscope images of silver nanoparticles formed in situ by dopamine chemistry.

The mussel inspired chemistry of dopamine oxidation to form polydopamine (PDA) and in situ reduction of metal ions in solution to form metal nanoparticles have widely opened the application of metal nanoparticles surface modification technology. This article contains the dataset of the scanning electron microscope (SEM) images of silver nanoparticles coated on polyethylene terephthalate (PET) films utilizing dopamine chemistry alone or combined with polyvinylpyrrolidone or glucose. The Ag NPs formed in various environments present round, cubic, or triangle shape. Mendeley Data, http://dx.doi.org/10.17632/bjjrt2dwbn.1.

Dynamic agent of an injectable and self-healing drug-loaded hydrogel for embolization therapy.

Embolic agents are crucial for trans-catheter arterial embolization (TAE) in the treatment of various unresectable malignant tumors. Although solid particles, liquid oils, and some polymeric hydrogels have proved their capacities for embolic therapies, the low efficiency, time sensitivity, and cytotoxicity are still considered as challenges. In this study, we developed a three-component dynamic self-healing hydrogel to overcome these limitations. With the help of the Schiff-base bonding, both glycol-chitosan and carbazochrome, containing amine groups, react with dibenzaldehyde-terminated poly(ethylene-glycol) (DF-PEG), forming the dynamic self-healing hydrogels under a mild condition within 200 s. 1H NMR and rheology test were used to characterize the Schiff-base formation and mechanical strength. Controlled-release of carbazochrome from different gelator concentrations of DF-PEG was also studied. Furthermore, in vivo evaluation of the embolization on rats showed the superior embolic effects of the injectable and self-healing hydrogel. Therefore, this new dynamic agent demonstrated the potential for application as a simple, inexpensive, and tunable embolic agent for cancer treatment and drug delivery system.

Morphological and molecular evidence for two new species in Lepiota from China.

Two new species in Lepiota sect. Ovisporae are described from tropical China. Lepiota angusticystidiata has a pileus with brownish yellow squamules covering a trichodermial palisade, ellipsoidal basidiospores, and narrowly clavate cheilocystidia; L. brunneosquamulosa has a tomentose, squamulose pileus with brownish yellow to yellowish brown concentric zones covering a trichodermial palisade, rarely with short elements, ellipsoidal or subcylindrical basidiospores with straight adaxial side, and no cheilocystidia. Phylogenetic relationships among species of sect. Ovisporae were inferred based on DNA sequences of the internal transcribed spacer region (ITS1-5.8S-ITS2 = ITS), the 5' end of the 28S gene (D1-D2-D3 variable domains), and partial sequences of the intergenic spacer (IGS1) of the nuc rDNA and the mitochondrial small ribosomal RNA gene (mtSSU), supporting the delineation of these new species.

Graphene-kaolin composite sponge for rapid and riskless hemostasis.

Kaolin is an effective and safe hemostatic agent for hemostasis. However, its ontic powder is difficult to use in actual practice. To develop a wieldy and powerful hemostat, composite strategy is usually a good choice. Herein, we developed a graphene-kaolin composite sponge (GKCS), synthesized with graphene oxide sheets, linker molecules and kaolin powders through a facile hydrothermal reaction. SEM observations support that GKCS has a porous structure, and EDS mapping further confirms that kaolin powders are embedded in graphene sheets. Once GKCS is exposed to bleeding, plasma is quickly absorbed inside the sponge, meanwhile blood cells are gathered at the interface. The gathered blood cells are in favor of accelerating clotting due to multi stimulations, including concentration, surface charge and activation of hemostatic factors, originating from both kaolin powders and graphene sponge. As a result, GKCS could stop bleeding in approximately 73 s in rabbit artery injury test. Besides, cytotoxicity and hemolysis assessments highlight that GKCS has a good biocompatibility. These remarkable properties suggest that GKCS is a potential riskless hemostatic agent for trauma treatment.

Cargo navigation across 3D microtubule intersections.

The eukaryotic cell's microtubule cytoskeleton is a complex 3D filament network. Microtubules cross at a wide variety of separation distances and angles. Prior studies in vivo and in vitro suggest that cargo transport is affected by intersection geometry. However, geometric complexity is not yet widely appreciated as a regulatory factor in its own right, and mechanisms that underlie this mode of regulation are not well understood. We have used our recently reported 3D microtubule manipulation system to build filament crossings de novo in a purified in vitro environment and used them to assay kinesin-1-driven model cargo navigation. We found that 3D microtubule network geometry indeed significantly influences cargo routing, and in particular that it is possible to bias a cargo to pass or switch just by changing either filament spacing or angle. Furthermore, we captured our experimental results in a model which accounts for full 3D geometry, stochastic motion of the cargo and associated motors, as well as motor force production and force-dependent behavior. We used a combination of experimental and theoretical analysis to establish the detailed mechanisms underlying cargo navigation at microtubule crossings.

Peptide oligomers from ultra-short peptides using sortase.

Sortase A catalyzed ligation of ultra-short peptides leads to inter/intra-molecular transpeptidation to form either linear or cyclic oligomers dependent upon the peptide length. Cyclic peptides were the main products for peptides with more than 15aa. However, for ultra-short (<15aa) peptides, cyclic oligomers became predominant in prolonged reactions. Peptides with 1-3 aminoglycines were equally active but peptide oligomers from peptide containing more than one aminoglycine were prone to hydrolysis.

High-Resolution Insights into the Stepwise Self-Assembly of Nanofiber from Bioactive Peptides.

Peptide self-assembly has a profound biological significance since self-assembled bioactive peptides are gifted with improved bioactivity as well as life-span. In this study, peptide self-assembly was investigated using a therapeutic peptide, PTP-7S (EENFLGALFKALSKLL). Combining experiments of atomic force microscopy (AFM), circular dichroism (CD), and 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence spectra, PTP-7S showed the α-helical structure and was found self-assembling into nanofibers in solution. Relying on the coarse-grained (CG) dynamic simulations, the self-assembling of PTP-7S was revealed as a stepwise process that peptide monomers first clustered into peptide-assembling units (PUs) with charged surface, and then the PUs integrated together to construct nanofibril aggregates. Different roles of the nonbonded driving forces did play in the two phases: the hydrophobic force and electrostatic interaction acted as the predominant motivations in the formation of PUs and nanofiber, respectively. Moreover, the electrostatic interaction helped to guide the longitudinal growth of peptide nanofibers. A sequence principle is proposed for peptide self-assembling in aqueous solution: a balance of the counter charges and sufficient hydrophobicity degree. The self-assembled PTP-7S displayed good anticancer activity, proteases resistance, and sustained drug-release, showing a great potential for clinical application. This study reveals the molecular mechanism in explaining PTP-7S self-assembly and it is beneficial for future innovation of the self-assembled bioactive peptides.

Preparation and anticancer activity evaluation of an amorphous drug nanocomposite by simple heat treatment.

The solubility of drug molecules is closely related to its bioactivity as it affects the dissolution rate and bioavailability, especially in the case of BCS IV drugs like camptothecin (CPT), a potential broad-spectrum anticancer agent. In this study, we construct a novel boric acid (BA)-coated CPT nanocomposite by means of a simple heat-treatment approach, which combines nanoscale size range and amorphous solid state together to improve the overall dissolution rate of CPT. This new CPT formulation showed a rod-like structure with nanoscale size and amorphous solid nature. These BA-coated CPT nanocomposites exhibited a dramatically improved dissolution rate, water dispersion property, and long-term chemical and physical stability. More importantly, the specific reactivity of BA groups to diols in the cell glycocalyx facilitated a rapid cross-membrane translocation of the drug nanocomposite, leading to efficient intracellular drug delivery. When tested on A549 cells and SKBR3 cells, this formulation demonstrated a much higher anticancer activity in comparison with free CPT, naked amorphous CPT nanoparticles, and control CPT nanocrystals. This formulation has great potential for clinical application; it is easy to scale up and be applied on other hydrophobic drugs.

A new targeted delivery approach by functionalizing drug nanocrystals through polydopamine coating.

Tumor target specificity via chemotherapy is widely considered to be very effective on tumor treatment. For an ideal chemotherapeutic agent like Camptothecin (CPT) (CPT is the abbreviation for Camptothecin), improved therapeutic efficacy and high selectivity are equally important. Inspired by adhesive proteins in mussels, here we developed a novel tumor targeting peptide XQ1 grafted CPT nanocrystals with polydopamine coating as a spacer. In this study, CPT nanocrystals were coated by polymerization of dopamine that was induced by plasma-activated water under an acidic environment, and then the tumor targeting peptide was grafted onto polydopamine (PDA) (PDA is the abbreviation for polydopamine) coated CPT nanocrystals through catechol chemistry. The PDA layer had negligible effects on drug crystallinity and structure but resulted in drug nanocrystals with excellent dispersion properties, improved dissolution rate and drug stability by preventing water hydrolysis. More importantly, tumor targeting peptide XQ1 facilitated a rapid cross-membrane translocation of drug nanocrystals via receptor-mediated endocytosis, leading to efficient intracellular drug delivery. Moreover, this novel drug formulation demonstrated more potent anti-cancer activity against tumor cells in comparison with free CPT and naked CPT nanocrystals and exhibited high selectivity, all of which are attributed to the tumor target specificity property and inherent pH-dependent drug release behavior.

Anti-cancer activity of camptothecin nanocrystals decorated by silver nanoparticles.

The emergence of multidrug resistant cancer phenotypes dramatically attenuates the efficiency of a variety of anti-cancer drugs. Silver nanoparticles (AgNPs) display excellent anti-cancer activity and dramatic inhibitory effect on drug resistance related proteins like P-glycoprotein (Pgp). Here we developed a novel drug nanocrystal formulation of Camptothecin (CPT), a broad spectrum anti-cancer agent, decorated by AgNPs. The resulting combinational formulation of CPT and AgNPs, named as CPT/Ag nanocrystals, demonstrated excellent dispersion properties and an improved dissolution rate, drug stability and cellular uptake rate. Because CPT nanocrystals are able to bypass Pgp recognition and AgNPs inhibit both Pgp expression and activity, CPT/Ag nanocrystals showed extreme and indiscriminate cytotoxicity against a variety of both drug sensitive and drug resistant cancer cells. Moreover, the quickly and plenty of released CPT from the CPT/Ag nanocrystals triggered by the tumor microenvironment led to a relaxed and cleavable chromatin structure, facilitating DNA damage and apoptotic potential of AgNPs that were subsequently released.

Enhanced anticancer activity of drug nanoparticles formulated with ß-cyclodextrin.

Camptothecin (CPT) is a potent chemotherapeutic agent that shows a broad spectrum of anticancer activities. However, it is clinically inactive because of poor aqueous solubility, rapid aqueous hydrolysis, and unexpected side effects. Three strategies have extensively been adopted to improve its dissolution rate including reduction of drug particle size to a nanoscale, use of an amorphous state, and the formation of inclusion compounds. In our study, we combined these three strategies together by constructing CPT nanoparticles by creating an inclusion complex with ß-cyclodextrin (BCD). This new CPT formulation showed a rod-like structure of nanoscaled size and with semiamorphous or amorphous CPT. These BCD-CPT nanoparticles showed improved dissolution rate, stability, dispersion, and cellular uptake. When tested on cancer cells, BCD-CPT nanoparticles showed a much higher anticancer activity (IC50=14-28 µmol/l) in comparison with free CPT (IC50>500 µmol/l) and CPT nanocrystals (IC50>200 µmol/l). In addition, BCD-CPT nanoparticles can be physically mixed with CPT nanocrystals, leading to CPT formulations with tailored drug-release profiles to achieve customized therapeutics and flexible treatments in clinics.

Extreme Activity of Drug Nanocrystals Coated with A Layer of Non-Covalent Polymers from Self-Assembled Boric Acid.

Non-covalent polymers have remarkable advantages over synthetic polymers for wide biomedical applications. In this study, non-covalent polymers from self-assembled boric acid were used as the capping reagent to replace synthetic polymers in drug crystallization. Under acidic pH, boric acid self-assembled on the surface of drug nanocrystals to form polymers with network-like structures held together by hydrogen bonds. Coating driven by boric acid self-assembly had negligible effects on drug crystallinity and structure but resulted in drug nanocrystals with excellent dispersion properties that aided in the formation of a more stable suspension. Boric acid coating improved drug stability dramatically by preventing drug molecules from undergoing water hydrolysis in a neutral environment. More importantly, the specific reactivity of orthoboric groups to diols in cell glycocalyx facilitated a rapid cross-membrane translocation of drug nanocrystals, leading to efficient intracellular drug delivery, especially on cancer cells with highly expressed sialic acids. Boric acid coated nanocrystals of camptothecin, an anticancer drug with poor aqueous solubility and stability, demonstrated extreme cytotoxic activity (IC50 < 5.0 µg/mL) to cancer cells compared to synthetic polymer coated CPT nanocrystals and free CPT. Surface coating using non-covalent polymers from self-assembled boric acid will have wide biomedical applications especially in biomaterials and drug delivery field.