RESUMEN
Recently, the development of anti-cancer approaches using different physical or chemical pathways has shifted from monotherapy to synergistic therapy, which can enhance therapeutic effects. As a result, enormous efforts have been devoted to developing various delivery systems encapsulated with dual agents for synergistic effects and to combat cancer cells acquired drug resistance. In this study, we show how to make Institute of Bioengineering and Nanotechnology (IBN)-1-based mesoporous silica nanoparticles (MSNs) for multifunctional drug delivery to overcome drug resistance cancer therapy. Initially, curcumin (Cur)-embedded IBN-1 nanocomposites (IBN-1-Cur) are synthesized in a simple one-pot co-condensation and then immobilized with the prodrug of Cisplatin (CP) on the carboxylate-modified surface (IBN-1-Cur-CP) to achieve photodynamic therapy (PDT) and chemotherapy in one platform, respectively, in the fight against multidrug resistance (MDR) of MES-SA/DX5 cancer cells. The Pluronic F127 triblock copolymer, as the structure-directing agent, in nanoparticles acts as a p-glycoprotein (p-gp) inhibitor. These designed hybrid nanocomposites with excellent structural properties are efficiently internalized by the endocytosis and successfully deliver Cur and CP molecules into the cytosol. Furthermore, the presence of Cur photosensitizer in the nanochannels of MSNs resulted in increased levels of cellular reactive oxygen species (ROS) under light irradiation. Thus, IBN-1-Cur-CP showed excellent anti-cancer therapy in the face of MES-SA/DX5 resistance cancer cells, owing to the synergistic effects of chemo- and photodynamic treatment.
RESUMEN
In order to interpret the clinical efficacy of conjugated ursodeoxycholate (UDC) in cholesterol (Ch) gallstone patients, the Ch solubilization in mixed micelles in 40:40:32 mM tauroursodeoxycholate (TUDC):taurochenodeoxycholate (TCDC):lecithin (L) and 80:32 mM TUDC:L systems was estimated by using a model of Ch binding to mixed micelles. The Ch solubilization limit in mixed TUDC:L micelles was found to be higher than that in mixed TUDC:TCDC:L micelles. In the 80:32 mM TUDC:L system, the dissolution of the Ch pellet decreased after vesicles (liposomes) formed on the surface of the Ch pellet whereas the dissolution of microcrystalline Ch was rapid before and after vesicle formation in the solution, indicating that the total surface area of solid Ch exposed to the solution may be another important factor in inducing the dissolution of Ch gallstones. These phenomena suggest that although vesicles, occasionally formed in the bile of patients under the therapy of conjugated UDC, make a contribution to the solubilization of Ch gallstones, the model of Ch binding to mixed TUDC:L micelles can be used to estimate Ch solubility in TUDC:L system.