A novel dendrimeric "glue" for adhesion of phosphatidyl choline-based liposomes

The interaction of phosphatidyl choline-cholesterol liposomes incorporating dihexadecyl phosphate as recognizable lipid with complementary guanidinylated diaminobutane poly(propylene imine) dendrimers of the fourth and fifth generation afforded liposome-dendrimer aggregates which were redispersed by the addition of an excess of a phosphate buffer. The higher generation dendrimeric derivative proved more effective when interacted with liposomes. This behavior was attributed to multivalent effects, which, as generally established, enhance the reactivity of multifunctional particles. Turbidimetry, atomic force microscopy (AFM) and optical microscopy were used for investigating the interaction of the complementary particles while the redispersion of the aggregates was studied by transmission electron microscopy (TEM). Liposomal membrane stability in the collapse and redispersion processes was assessed by the calcein fluorescence method, TEM, and AFM

Factors mediating lipofection potency of a series of cationic phosphonolipids in human cell lines

A series of cationic liposomes known as cationic phosphonolipids (CPs) were evaluated as vehicles for in vitro gene transfer in K562 erythroleukemia cells and 5637 epithelial carcinoma cells. For each CP and target cell type examined, detailed analyses were performed to determine optimal transfection conditions (lipid/ DNA (+/-) charge ratio, amount of complexed episomal DNA, liposomal and lipoplex size, complexation medium and duration of complex-cell exposure time). Lipofection conditions were determined to be both cell- and lipid-type specific. Complexation medium critically affected transfection competence. The initial size of the liposome was not always predictive of lipofection potency. The lipid chemical composition had a strong impact upon lipofection efficiency; DOPE inclusion in the liposome formulations was found to affect the levels of transgene expression in a cell-dependent way. Notably, effective transgene expression was characterized by prominent plasmid nuclear incorporation. Human Aγ- and ε-globin transgene nuclear incorporation and expression in 5637 cells post GLB.391-mediated lipofection lends credence to its use as a vehicle of therapeutic transgene delivery. © 2006 Elsevier B.V. All rights reserved

Targeting breast cancer stem-like cells using chloroquine encapsulated by a triphenylphosphonium-functionalized hyperbranched polymer

Cancer stem cells (CSCs) have garnered increasing attention over the past decade, as they are believed to play a crucial role in tumor progression and drug resistance. Accumulating evidence provides insight into the function of autophagy in maintenance and survival of CSCs. Here, we studied the impact of a mitochondriotropic triphenylphosphonium-functionalized dendrimeric nanocarrier on cultured breast cancer cell lines, grown either as adherent cells or as mammospheres that mimic a stem-like phenotype. The nanocarrier manifested a substantial cytotoxicity both alone as well as after encapsulation of chloroquine, a well-known autophagy inhibitor. The cytotoxic effects of the nanocarrier could be ascribed to interference with mitochondrial function. Importantly, mammospheres were selectively sensitive to encapsulated chloroquine and this depends on the expression of the gene encoding ATM kinase. Ataxia-telangiectasia mutated (ATM) kinase is an enzyme that functions as an essential signaling mediator that enables growth of cancer stem cells through the regulation of autophagy. We noted that this ATM-dependent sensitivity of mammospheres to encapsulated chloroquine was independent of the status of the tumor suppressor gene p53. Our study suggests that breast cancer stem cells, as they are modeled by mammospheres, are sensitive to encapsulated chloroquine, depending on the expression of the ATM kinase, which is thereby characterized as a potential biomarker for sensitivity to this type of treatment. © 2020 Elsevier B.V

Modified Carbon Nanostructures As Catalysts For Oxygen Reduction Reaction

This work is oriented to take advantage of graphene and nanotubes features in electrocatalysis. At present, a main challenge in this context deals with obtaining inexpensive, energetically efficient and durable catalysts for oxygen reduction in Polymer Electrolyte Membrane Fuel Cells (PEMFC). Platinum and Pt-alloys are currently the best cathode catalysts for this reaction. However, since the metal is scarce and expensive, there is a strong effort to find alternative catalysts. Nitrogen-doped carbon catalysts, also containing iron and cobalt centres, appear to be good and promising platinum alternatives1. For outstanding electronic, mechanical and structural properties graphene oxide and nanotubes could be extremely interesting substitutes either as a catalyst itself or as catalyst support. In this work, we will present some preliminary electrochemical results on Oxygen Reduction Reaction about a series of graphene oxide intercalated with polyethyleneimine of different molecular weight2 and doped with iron, and iron doped nitrogen modified nanotubes, prepared using different nitrogen insertion methods. Physico-chemical characterisation will be also presented. 1 F. Jaouen, V. Goellner, M. Lefevre, J. Herranz, E. Proietti, J.P. Dodelet, Electrochim. Acta 87 (2013) 619. 2 T. Tsoufis, F. Katsaros, Z. Sideratou, B.J. Kooi, M.A. Karakassides, A. Siozios, Chem. A Eur. J., In Press, DOI: 10.1002/chem.201304599

Factors mediating lipofection potency of a series of cationic phosphonolipids in human cell lines

A series of cationic liposomes known as cationic phosphonolipids (CPs) were evaluated as vehicles for in vitro gene transfer in K562 erythroleukemia cells and 5637 epithelial carcinoma cells. For each CP and target cell type examined, detailed analyses were performed to determine optimal transfection conditions (lipid/ DNA (+/-) charge ratio, amount of complexed episomal DNA, liposomal and lipoplex size, complexation medium and duration of complex-cell exposure time). Lipofection conditions were determined to be both cell- and lipid-type specific. Complexation medium critically affected transfection competence. The initial size of the liposome was not always predictive of lipofection potency. The lipid chemical composition had a strong impact upon lipofection efficiency; DOPE inclusion in the liposome formulations was found to affect the levels of transgene expression in a cell-dependent way. Notably, effective transgene expression was characterized by prominent plasmid nuclear incorporation. Human Aγ- and ε-globin transgene nuclear incorporation and expression in 5637 cells post GLB.391-mediated lipofection lends credence to its use as a vehicle of therapeutic transgene delivery. © 2006 Elsevier B.V. All rights reserved

In situ growth of capping-free magnetic iron oxide nanoparticles on liquid-phase exfoliated graphene

We report a facile approach for the in situ synthesis of very small iron oxide nanoparticles on the surface of high-quality graphene sheets. Our synthetic strategy involved the direct, liquid-phase exfoliation of highly crystalline graphite (avoiding any oxidation treatment) and the subsequent chemical functionalization of the graphene sheets via the well-established 1,3-dipolar cycloaddition reaction. The resulting graphene derivatives were employed for the immobilization of the nanoparticle precursor (Fe cations) at the introduced organic groups by a modified wet-impregnation method, followed by interaction with acetic acid vapours. The final graphene-iron oxide hybrid material was achieved by heating (calcination) in an inert atmosphere. Characterization by X-ray diffraction, transmission electron and atomic force microscopy, Raman and X-ray photoelectron spectroscopy gave evidence for the formation of rather small (<12 nm), spherical, magnetite-rich nanoparticles which were evenly distributed on the surface of few-layer (<1.2 nm thick) graphene. Due to the presence of the iron oxide nanoparticles, the hybrid material showed a superparamagnetic behaviour at room temperature

A triphenylphosphonium-functionalized mitochondriotropic nanocarrier for efficient co-delivery of doxorubicin and chloroquine and enhanced antineoplastic activity

Drug delivery systems that target subcellular organelles and, in particular, mitochondria are considered to have great potential in treating disorders that are associated with mitochondrial dysfunction, including cancer or neurodegenerative diseases. To this end, a novel hyperbranched mitochondriotropic nanocarrier was developed for the efficient co-delivery of two different (both in chemical and pharmacological terms) bioactive compounds. The carrier is based on hyperbranched poly(ethyleneimine) functionalized with triphenylphosphonium groups that forms ~100 nm diameter nanoparticles in aqueous media and can encapsulate doxorubicin (DOX), a well-known anti-cancer drug, and chloroquine (CQ), a known chemosensitizer with arising potential in anticancer medication. The anticancer activity of this system against two aggressive DOX-resistant human prostate adenocarcinoma cell lines and in in vivo animal studies was assessed. The co-administration of encapsulated DOX and CQ leads to improved cell proliferation inhibition at extremely low DOX concentrations (0.25 μM). In vivo experiments against DU145 human prostate cancer cells grafted on immunodeficient mice resulted in tumor growth arrest during the three-week administration period and no pervasive side effects. The findings put forward the potential of such targeted low dose combination treatments as a therapeutic scheme with minimal adverse effects. © 2017 by the authors. Licensee MDPI, Basel, Switzerland