Search

A dual drug-loaded HNT–CD glycocluster delivery system based on halloysite nanotubes and carbohydrate functionalized cyclodextrin was developed by a green protocol using solvent-free microwave irradiation. The nanohybrid was employed for concurrent load and release of silibinin and curcumin. The new delivery system was characterized by means of TGA, FT-IR spectroscopy, SEM and DLS. These techniques confirm the successful loading of the two drugs in the system. SEM and DLS measurements highlighted that the nanomaterial preserves a tubular structure with an average hydrodynamic radius of ca. 200 nm. The release of the drugs from the HNT glycocluster was investigated by means of UV-vis spectroscopy at two different pH values simulanting the typical physiological conditions of either gastric or intestinal fluids. Enzyme-linked lectin assays (ELLA) demonstrated that highly mannoside–cyclodextrins HNT entities display high affinity towards mannose selective ConA lectin. Biological assays showed that the new drug delivery system exhibits anti-proliferative activity against the investigated cell lines. Fluorescence microscopy confirmed ELLA results and it showed a high propensity of this drug delivery system to cross cell membranes and to penetrate into the cell nucleus. The results revealed that the synthesized multicavity system is a material of suitable size and nanoarchitecture to transport drugs into living cells.

Neuroserpin (NS) is a serpin inhibitor of tissue plasminogen activator (tPA) in the brain. The polymerisation of NS pathologic mutants is responsible for a genetic dementia known as familial encephalopathy with neuroserpin inclusion bodies (FENIB). So far, a pharmacological treatment of FENIB, i.e. an inhibitor of NS polymerisation, remains an unmet challenge. Here, we present a biophysical characterisation of the effects caused by embelin (EMB a small natural compound) on NS conformers and NS polymerisation. EMB destabilises all known NS conformers, specifically binding to NS molecules with a 1:1 NS:EMB molar ratio without unfolding the NS fold. In particular, NS polymers disaggregate in the presence of EMB, and their formation is prevented. The NS/EMB complex does not inhibit tPA proteolytic activity. Both effects are pharmacologically relevant: firstly by inhibiting the NS polymerisation associated to FENIB, and secondly by potentially antagonizing metastatic processes facilitated by NS activity in the brain.

A dual drug-loaded HNT–CD glycocluster delivery system based on halloysite nanotubes and carbohydrate functionalized cyclodextrin was developed by a green protocol using solvent-free microwave irradiation. The nanohybrid was employed for concurrent load and release of silibinin and curcumin. The new delivery system was characterized by means of TGA, FT-IR spectroscopy, SEM and DLS. These techniques confirm the successful loading of the two drugs in the system. SEM and DLS measurements highlighted that the nanomaterial preserves a tubular structure with an average hydrodynamic radius of ca. 200 nm. The release of the drugs from the HNT glycocluster was investigated by means of UV-vis spectroscopy at two different pH values simulanting the typical physiological conditions of either gastric or intestinal fluids. Enzyme-linked lectin assays (ELLA) demonstrated that highly mannoside–cyclodextrins HNT entities display high affinity towards mannose selective ConA lectin. Biological assays showed that the new drug delivery system exhibits anti-proliferative activity against the investigated cell lines. Fluorescence microscopy confirmed ELLA results and it showed a high propensity of this drug delivery system to cross cell membranes and to penetrate into the cell nucleus. The results revealed that the synthesized multicavity system is a material of suitable size and nanoarchitecture to transport drugs into living cells.

A dual drug-loaded HNT–CD glycocluster delivery system based on halloysite nanotubes and carbohydrate functionalized cyclodextrin was developed by a green protocol using solvent-free microwave irradiation. The nanohybrid was employed for concurrent load and release of silibinin and curcumin. The new delivery system was characterized by means of TGA, FT-IR spectroscopy, SEM and DLS. These techniques confirm the successful loading of the two drugs in the system. SEM and DLS measurements highlighted that the nanomaterial preserves a tubular structure with an average hydrodynamic radius of ca. 200 nm. The release of the drugs from the HNT glycocluster was investigated by means of UV-vis spectroscopy at two different pH values simulanting the typical physiological conditions of either gastric or intestinal fluids. Enzyme-linked lectin assays (ELLA) demonstrated that highly mannoside–cyclodextrins HNT entities display high affinity towards mannose selective ConA lectin. Biological assays showed that the new drug delivery system exhibits anti-proliferative activity against the investigated cell lines. Fluorescence microscopy confirmed ELLA results and it showed a high propensity of this drug delivery system to cross cell membranes and to penetrate into the cell nucleus. The results revealed that the synthesized multicavity system is a material of suitable size and nanoarchitecture to transport drugs into living cells.

A dual drug-loaded HNT–CD glycocluster delivery system based on halloysite nanotubes and carbohydrate functionalized cyclodextrin was developed by a green protocol using solvent-free microwave irradiation. The nanohybrid was employed for concurrent load and release of silibinin and curcumin. The new delivery system was characterized by means of TGA, FT-IR spectroscopy, SEM and DLS. These techniques confirm the successful loading of the two drugs in the system. SEM and DLS measurements highlighted that the nanomaterial preserves a tubular structure with an average hydrodynamic radius of ca. 200 nm. The release of the drugs from the HNT glycocluster was investigated by means of UV-vis spectroscopy at two different pH values simulanting the typical physiological conditions of either gastric or intestinal fluids. Enzyme-linked lectin assays (ELLA) demonstrated that highly mannoside–cyclodextrins HNT entities display high affinity towards mannose selective ConA lectin. Biological assays showed that the new drug delivery system exhibits anti-proliferative activity against the investigated cell lines. Fluorescence microscopy confirmed ELLA results and it showed a high propensity of this drug delivery system to cross cell membranes and to penetrate into the cell nucleus. The results revealed that the synthesized multicavity system is a material of suitable size and nanoarchitecture to transport drugs into living cells.

A dual drug-loaded HNT–CD glycocluster delivery system based on halloysite nanotubes and carbohydrate functionalized cyclodextrin was developed by a green protocol using solvent-free microwave irradiation. The nanohybrid was employed for concurrent load and release of silibinin and curcumin. The new delivery system was characterized by means of TGA, FT-IR spectroscopy, SEM and DLS. These techniques confirm the successful loading of the two drugs in the system. SEM and DLS measurements highlighted that the nanomaterial preserves a tubular structure with an average hydrodynamic radius of ca. 200 nm. The release of the drugs from the HNT glycocluster was investigated by means of UV-vis spectroscopy at two different pH values simulanting the typical physiological conditions of either gastric or intestinal fluids. Enzyme-linked lectin assays (ELLA) demonstrated that highly mannoside–cyclodextrins HNT entities display high affinity towards mannose selective ConA lectin. Biological assays showed that the new drug delivery system exhibits anti-proliferative activity against the investigated cell lines. Fluorescence microscopy confirmed ELLA results and it showed a high propensity of this drug delivery system to cross cell membranes and to penetrate into the cell nucleus. The results revealed that the synthesized multicavity system is a material of suitable size and nanoarchitecture to transport drugs into living cells.

A dual drug-loaded HNT–CD glycocluster delivery system based on halloysite nanotubes and carbohydrate functionalized cyclodextrin was developed by a green protocol using solvent-free microwave irradiation. The nanohybrid was employed for concurrent load and release of silibinin and curcumin. The new delivery system was characterized by means of TGA, FT-IR spectroscopy, SEM and DLS. These techniques confirm the successful loading of the two drugs in the system. SEM and DLS measurements highlighted that the nanomaterial preserves a tubular structure with an average hydrodynamic radius of ca. 200 nm. The release of the drugs from the HNT glycocluster was investigated by means of UV-vis spectroscopy at two different pH values simulanting the typical physiological conditions of either gastric or intestinal fluids. Enzyme-linked lectin assays (ELLA) demonstrated that highly mannoside–cyclodextrins HNT entities display high affinity towards mannose selective ConA lectin. Biological assays showed that the new drug delivery system exhibits anti-proliferative activity against the investigated cell lines. Fluorescence microscopy confirmed ELLA results and it showed a high propensity of this drug delivery system to cross cell membranes and to penetrate into the cell nucleus. The results revealed that the synthesized multicavity system is a material of suitable size and nanoarchitecture to transport drugs into living cells.

Neuroserpin (NS) is a serpin inhibitor of tissue plasminogen activator (tPA) in the brain. The polymerisation of NS pathologic mutants is responsible for a genetic dementia known as familial encephalopathy with neuroserpin inclusion bodies (FENIB). So far, a pharmacological treatment of FENIB, i.e. an inhibitor of NS polymerisation, remains an unmet challenge. Here, we present a biophysical characterisation of the effects caused by embelin (EMB a small natural compound) on NS conformers and NS polymerisation. EMB destabilises all known NS conformers, specifically binding to NS molecules with a 1:1 NS:EMB molar ratio without unfolding the NS fold. In particular, NS polymers disaggregate in the presence of EMB, and their formation is prevented. The NS/EMB complex does not inhibit tPA proteolytic activity. Both effects are pharmacologically relevant: firstly by inhibiting the NS polymerisation associated to FENIB, and secondly by potentially antagonizing metastatic processes facilitated by NS activity in the brain.

Cancer stem cell characterization represents a breakthrough in cancer research. Despite evidence showing the existence and the role of cancer stem cells in osteosarcoma (OS) onset and progression, little is known about their specific surface phenotype. To address this issue, we carried out a cytometric analysis with an antibody-array comprising 245 membrane proteins comparing the stem and differentiated OS cells. As experimental model, we chose the stem-like cell line 3aminobenzamide-OS and its parental, differentiated, cell line MG63. We identified 50 differentially expressed, 23 homogeneously expressed, and 172 not expressed proteins in the two cell line models, thus defining a surface protein signature specific for each of them. Furthermore, we selected ERK1/2 (p44/42 mitogen-activated protein kinases) as a potential pathway correlated with processes that characterize tumorigenic potential and stemness of 3aminobenzamide-OS cells

BACKGROUND: Despite the well recognized expression of the cell surface markers cluster of differentiation 44 (homing cell adhesion molecule) and CD133 (Prominin 1) on human colorectal cancer stem cells (CCSCs), these molecules do not appear to be effective targets for stem cell-directed therapies. Because the surface marker CD66c (also known as carcinoembryonic antigen-related cell adhesion molecule 6) has demonstrated promise as a therapeutic target in pancreatic malignancy, the authors evaluated its potential as a target for stem cell-directed treatment of colorectal cancer. METHODS: First, the authors characterized CD66c expression by flow cytometry and immunohistochemistry in colon cancer samples and in normal colon tissues. Then, the coexpression of CD66c and CD133 was evaluated on putative CCSCs. CD66c expression also was measured in stem cell-enriched colon spheres. Finally, the effects of small-interfering RNA-mediated CD66c silencing on the in vitro and in vivo growth of Caco2 colon cancer cells were evaluated. RESULTS: CD66c expression was significantly higher in colon cancers than in contiguous normal colon tissues and paralleled cancer stage. CD66c was absent in CD133-positive cells that were isolated from normal colon, whereas its expression was brightest (CD66cbright) in CD133-positive cells from colon cancer samples. In vitro experiments demonstrated that colon spheres were considerably enriched in a CD66cbright population in a fashion comparable to the enrichment observed in fresh liver metastases. In vitro proliferation and clonogenic potential were hampered when CD66c was silenced in Caco2 cells. Finally, in vivo xenograft experiments demonstrated that CD66c silencing almost completely abrogated the tumorigenic potential of Caco2 cells. CONCLUSIONS: CD66cbright expression was associated with colon cancer stem cells and CD66c silencing blocked tumor growth, thereby opening the way to a potential new treatment for colon cancer. Cancer 2013.

This patent application pertains to a routing method implemented in the stored programs of a digital computer which is programmably operated to generate the wire interconnect masks for a two level metallization automated universal array having undefined roadbeds between rows of cells comprised of identical semiconductor device basic units which are futher interconnected to provide a particular integrated circuit structure. Conductor routing is provided by a computer aided design system that, among other things, carries out a route analysis process which determines in which roadbed each wire should be tentatively routed in conjunction with generating a routing density profile for minimizing congestion for a particular circuit design and when the roadbed density is exceeded, certain wires are removed under a set of criteria for routing by a pathfinder routing process. Following route analysis, detailed routing and rerouting is performed sequentially by a direct routing process, a greedy channel routing process, and a pathfinder routing process with rerouting being performed after each channel router and pathfinding process. Furthermore, the greedy channel routing process makes a single pass from left to right in all wires which cross successive points simultaneously and, if necessary, deleting a wire or wires which are then rerouted by the pathfiniding process.