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•GKCS rapidly stops bleeding in approximately 73 s in rabbit artery injury test.•Hemolysis and cytotoxicity assays demonstrate GKCS’ biocompatibility.•Synergic mechanism on bleeding ...control is discussed.•It is a facile and efficient method to make a hemostatic composite.•GKCS is a new Kaolin-based or graphene-based 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.
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.
Indwelling device infections now represent life-threatening circumstances as a result of the biofilms' tolerance to antibiotic treatments. Current antibiotic impregnation approaches through sustained ...antibiotic release have some unsolved problems which include short life-span, narrowed antibacterial spectrum, ineffectiveness towards resistant mutants, and the potential to hasten the antibiotic resistance process. In this study, bacteria responsive anti-biofilm surfaces were developed using bioactive peptides with proved activity to antibiotic resistant bacteria and biofilms. Resulting surfaces were stable under physiological conditions and in the presence of high concentrations of salts (0.5M NaCl) and biomacromolcules (1.0% DNA and 2.0% alginate), and thus showed good biocompatibility to various tissue cells. However, lytic peptide immobilized surfaces could sense bacteria adhesion and kill attached bacteria effectively and specifically, so biofilms were unable to develop on the lytic peptide immobilized surfaces. Bacteria responsive catheters remained biofilm free for up to a week. Therefore, the bacteria responsive antibacterial surfaces developed in this study represent new opportunities for indwelling device infections.
Biofilm associated indwelling device infections represent life-threatening circumstances. Current antibiotic impregnation approaches through sustained antibiotic release have some unsolved problems. In this study, bacteria responsive anti-biofilm surfaces were developed using peptides with proved activity to antibiotic resistant bacteria and biofilms. Bacteria responsible catheters maintained biofilm free during a week of continuous cultivation. Display omitted
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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.
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•The single needle electrospraying method is used to prepare the double-walled PHNP microspheres.•PVA hydrogel acts as the inner layer packaged by the PCL outer layer.•The volume ...ratio between PVA and PCL determines the size and morphology of the PHNP microsphere.•This PHNP microsphere shows high drug loading capacity and slow drug release.•The biocompatible PHNP is a promising drug delivery carrier for cancer treatment.
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.
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•A three competitive method was established to calculate the binding constant.•This approach is suitable for all types of guest molecules tested.•This assay works in solutions within ...a wide pH range close to the physiological pH.
Cyclodextrins are capable of forming host-guest inclusion complexes with a variety of guest molecules. However, binding constant measurements of various host-guest inclusions require complex equipment like NMR. Current methods may make binding constant measurement extremely difficult or even impossible for some guest molecules with specific or complicated structures. In this paper, we discovered a new method to determine the binding constants of complexes between β-Cyclodextrin and guest molecules using an inducible fluorophore, Alizarin Red S. The β-Cyclodextrin binding constants of various guest molecules including amino acids, anticancer drugs, antibiotics, and peptides were calculated according to the competition method. This novel florescence spectroscopic technique is reliable and reproducible, and represents an easy and accurate way for β-Cyclodextrin-guest binding constants measurement.
Lepiota sect. Stenosporae (J.E. Lange) Kühner contains species with spurred or truncate basidiospores and pileus covering composed of adnate, ascending or erect long and slender elements. Seven ...species from southwestern, northeastern and southern China in this section have been identified, described and illustrated. Lepiota mandarina and L. subcastanea are described as new. Lepiota mandarina is characterized by densely orange red to brownish red squamules on pileus and stipe, subtriangular basidiospores with truncate bottom, narrowly clavate cheilocystidia and pileus covering a trichodermial palisade. Lepiota subcastanea has a pileus with yellow-brown to dark brown squamules, non-dextrinoid subtriangular basidiospores with a distinct sac-like spur, narrowly clavate or narrowly utriform cheilocystidia, and pileus covering a trichodermial palisade with short clavate elements. It is hypothesized that this section evolved from sect. Ovisporae subsect. Helveolinae. It also is speculated that subtriangular and spurred basidiospores have evolved from ellipsoidal basidiospores and that a trichodermial pileus covering composing long, erect elements and basal short, clavate elements might have evolved from a cutis or a trichoderm lacking such an under layer of short elements.
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 (IC
< 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.
Peptides have some unique and superior features compared to proteins. However, the use of peptides as therapeutics is hampered by their low stability and cell selectivity. In this study, a new lytic ...peptide (CL-1, FLGALFRALSRLL) was constructed. Under the physiological condition, peptide CL-1 self-assembled into dynamically stable aggregates with fibrils-like structures. Aggregated CL-1 demonstrated dramatically altered activity and stability in comparison with single molecule CL-1 and other lytic peptides: when incubated with cocultured bacteria and tissue cells, CL-1 aggregates killed bacteria selectively but spared cocultured human cells; CL-1 aggregates were kept intact in human serum for more than five hours. Peptide-cell interaction studies performed on lipid monolayers and live human tissue cells revealed that in comparison with monomeric CL-1, aggregated CL-1 had decreased cell affinity and membrane insertion capability on tissue cells. A dynamic process involving aggregate dissociation and rearrangement seemed to be an essential step for membrane bound CL-1 aggregates to realize its cytotoxicity to tissue cells. Our study suggests that peptide aggregation could be as important as the charge and secondary structure of a peptide in affecting peptide-cell interactions. Controlling peptide self-assembly represents a new way to increase the stability and cell selectivity of bioactive peptides for wide biomedical applications.
Current processes for surface coating by nano-metals must be performed at extreme conditions and require the use of sophisticated instruments. Herein, we developed a new method of polydopamine ...(PDA)-enabled surface coating with nano-metals by combining PDA surface coating and PDA-enabled metal ions reduction with PDA removal by argon plasma afterwards. The size and density of the metal nanoparticles (MNPs) could be tuned easily by controlling the amount (and thickness) of PDA coating layers, metal ions concentration, and reduction time as demonstrated in surface coating with silver or gold nanoparticles. Resulting MNPs coated surfaces were characterized through scanning electron microscope (SEM), spectrophotometer, and X-ray Diffractometer (XRD). One application in surface enhanced Raman scattering (SERS) to detect rhodamine 6G (R6G) molecule is demonstrated. This new and simple technology of polydopamine-enabled surface coating with nano-metals should have wide applications.
•Reduction of metal ions by polydopamine (PDA) on material surfaces to form metal nanoparticles (MNPs).•Removal of the PDA layer from MNPs coated surfaces by argon plasma.•PDA reduction in combination with plasma etching represents a new and tunable surface nano-metals coating technology.•Application of this PDA-mediated surface nano-coatings was illustrated with Surface enhanced Raman scattering technique.
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