ABSTRACT
Multidrug resistance (MDR) is the leading cause of failure for breast cancer in the clinic. Thus far, polymer-lipid hybrid nanoparticles (PLN) loaded chemotherapeutic agents has been used to overcome MDR in breast cancer. In this study, we prepared psoralen polymer-lipid hybrid nanoparticles (PSO-PLN) to reverse drug resistant MCF-7/ADR cells in vitro and in vivo. PSO-PLN was prepared by the emulsification evaporation-low temperature solidification method. The formulation, water solubility and bioavailability, particle size, zeta potential and entrapment efficiency, and in vitro release experiments were optimized in order to improve the activity of PSO to reverse MDR. Optimal formulation: soybean phospholipids 50 mg, poly(lactic-co-glycolic) acid (PLGA) 15 mg, PSO 3 mg, and Tween-80 1%. The PSO-PLN possessed a round appearance, uniform size, exhibited no adhesion. The average particle size was 93.59 ± 2.87 nm, the dispersion co-efficient was 0.249 ± 0.06, the zeta potential was 25.47 ± 2.84 mV. In vitro analyses revealed that PSO resistance index was 3.2, and PSO-PLN resistance index was 5.6, indicating that PSO-PLN versus MCF-7/ADR reversal effect was significant. Moreover, PSO-PLN is somewhat targeted to the liver, and has an antitumor effect in the xenograft model of drug-resistant MCF-7/ADR cells. In conclusion, PSO-PLN not only reverses MDR but also improves therapeutic efficiency by enhancing sustained release of PSO.
Subject(s)
Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Ficusin/chemistry , Ficusin/pharmacology , Lipids/chemistry , Nanoparticles/chemistry , Polymers/chemistry , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Biological Availability , Breast Neoplasms/drug therapy , Cell Line, Tumor , Chemistry, Pharmaceutical/methods , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacology , Drug Liberation/drug effects , Female , Humans , Lactic Acid/chemistry , MCF-7 Cells , Mice , Mice, Inbred BALB C , Mice, Nude , Particle Size , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Solubility/drug effectsABSTRACT
AlgE is an outer membrane protein present in alginate-producing (mucoid) Pseudomonas aeruginosa. AlgE has been overexpressed in insoluble inclusion bodies, purified under denaturing conditions and refolded in a buffer containing decyl beta-D-maltopyranoside. Purified refolded AlgE was detergent-exchanged into n-octyl tetraoxyethylene and diffraction-quality crystals were grown using the hanging-drop vapor-diffusion method. The crystals grew as small hexagons with unit-cell parameters a = 98.8, b = 156.8, c = 90.4 A, alpha = beta = gamma = 90.0 degrees . The crystals exhibited the symmetry of space group C222 and diffracted to a minimum d-spacing of 3.0 A. On the basis of the Matthews coefficient (V(M) = 3.28 A(3) Da(-1)), one molecule is estimated to be present in the asymmetric unit.
Subject(s)
Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Gene Expression , Protein Folding , Pseudomonas aeruginosa/chemistry , Pseudomonas aeruginosa/metabolism , Alginates , Bacterial Proteins/analysis , Bacterial Proteins/genetics , Crystallization , Crystallography, X-Ray , Glucuronic Acid/biosynthesis , Hexuronic Acids , Pseudomonas aeruginosa/geneticsABSTRACT
Fe-catalyzed cross-coupling reactions between a bicyclic alkenyl triflate and Grignard reagents were investigated. Under the optimized reaction conditions, various 2-substituted bicyclic alkenes were synthesized in moderate to excellent yields (52-93%). This method provided an efficient route for the synthesis of 2-substituted bicyclic alkenes with secondary alkyl groups which cannot be synthesized using previous methods such as Pd-catalyzed coupling reactions and lithium-halide exchange reactions.
