608136-12-5Relevant articles and documents
Docetaxel-Loaded Fluorescent Liquid-Crystalline Nanoparticles for Cancer Theranostics
Meli, Valeria,Caltagirone, Claudia,Falchi, Angela M.,Hyde, Stephen T.,Lippolis, Vito,Monduzzi, Maura,Obiols-Rabasa, Marc,Rosa, Antonella,Schmidt, Judith,Talmon, Yeshayahu,Murgia, Sergio
, p. 9566 - 9575 (2015)
Here, we describe a novel monoolein-based cubosome formulation engineered for possible theranostic applications in oncology. The Docetaxel-loaded nanoparticles were stabilized in water by a mixture of commercial Pluronic (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer) F108 (PF108) and rhodamine- and folate-conjugated PF108 so that the nanoparticles possess targeting, therapeutic, and imaging properties. Nanoparticles were investigated by DLS, cryo-TEM, and SAXS to confirm their structural features. The fluorescent emission characterization of the proposed formulation indicated that the rhodamine conjugated to the PF108 experiences an environment less polar than water (similar to chloroform), suggesting that the fluorescent fragment is buried within the poly(ethylene oxide) corona surrounding the nanoparticle. Furthermore, these nanoparticles were successfully used to image living HeLa cells and demonstrated a significant short-term (4 h incubation) cytotoxicity effect against these cancer cells. Furthermore, given their analogy as nanocarriers for molecules of pharmaceutical interest and to better stress the singularities of these bicontinuous cubic nanoparticles, we also quantitatively evaluated the differences between cubosomes and multilamellar liposomes in terms of surface area and hydrophobic volume.
Activity-based proteome profiling of potential cellular targets of orlistat - An FDA-approved drug with anti-tumor activities
Yang, Peng-Yu,Liu, Kai,Ngai, Mun Hong,Lear, Martin J.,Wenk, Markus R.,Yao, Shao Q.
supporting information; scheme or table, p. 656 - 666 (2010/03/25)
Orlistat, or tetrahydrolipstatin (THL), is an FDA-approved antiobesity drug with potential antitumor activities. Cellular off-targets and potential side effects of Orlistat in cancer therapies, however, have not been extensively explored thus far. In this study, we report the total of synthesis of THL-like protein-reactive probes, in which extremely conservative modifications (i.e., an alkyne handle) were introduced in the parental THL structure to maintain the native biological properties of Orlistat, while providing the necessary functionality for target identification via the bio-orthogonal click chemistry. With these natural productlike, cell-permeable probes, we were able to demonstrate, for the first time, this chemical proteomic approach is suitable for the identification of previously unknown cellular targets of Orlistat. In addition to the expected fatty acid synthase (FAS), we identified a total of eight new targets, some of which were further validated by experiments including Western blotting, recombinant protein expression, and site-directed mutagenesis. Our findings have important implications in the consideration of Orlistat as a potential anticancer drug at its early stages of development for cancer therapy. Our strategy should be broadly useful for off-target identification against quite a number of existing drugs and/or candidates, which are also covalent modifiers of their biological targets.
Practical synthetic route to functionalized rhodamine dyes
Nguyen, Trung,Francis, Matthew B.
, p. 3245 - 3248 (2007/10/03)
(Matrix presented) An efficient method for the synthesis of functionalized rhodamine derivatives has been developed. Multigram quantities of these water-soluble fluorophores can be prepared from inexpensive precursors and purified without the use of chromatography. A series of protein-reactive functional groups has been installed through subsequent reactions, providing materials for biomolecule modification. For multicolor applications, a solid-phase purification strategy has been developed to afford rhodamine derivatives possessing a wide range of spectral properties.
