Co-delivery of Cyclopamine and Doxorubicin Mediated by Bovine Serum Albumin Nanoparticles Reverses Doxorubicin Resistance in Breast Cancer by Down-regulating P-glycoprotein Expression.

Combination chemotherapy is considered to be one of the most effective treatments for breast cancer by reducing the emergence of drug resistance. In this study, a novel drug delivery system based on bovine serum albumin nanoparticles (BSA NPs) was successfully developed. Doxorubicin (DOX) and cyclopamine (CYC), a potential anti-cancer agent that inhibits the hedgehog signaling pathway were entrapped into BSA NPs through electrostatic interactions and hydrophobic interactions, respectively. Rather than simple combination of two different chemotherapeutics, the CYC also increased the intracellular DOX accumulation by decreasing the expression of P-glycoprotein (P-gp), which could thus reverse the DOX resistance. Tumor-targeting property of nanoparticles was the prerequisite for its further application. Interestingly, retention of fluorescently-labeled particles in vivo indicated that the dual-drug-loaded BSA NPs could not only target the primary tumors, but also target the metastatic lymph nodes, which would simultaneously inhibit the tumor growth and distant metastasis. Taken together, this study provides a promising strategy for co-delivery of drugs, tumor and metastatic lymph node targeting, and DOX resistance reversing in breast cancer chemotherapy.

[Effect of Zirconium-modified Zeolite Addition on Phosphorus Release and Immobilization in Heavily Polluted River Sediment].

The effect of zirconium-modified zeolite (ZrMZ) addition on the release and immobilization of phosphorus in heavily polluted river sediment was investigated using microcosm incubation experiments. Results showed that addition of ZrMZ to sediment greatly reduced concentrations of P in pore water and overlying water, also reducing the release flux of P across the interface between overlying water and sediment. The addition of ZrMZ to sediment resulted in the transformation of NH4Cl extractable P (NH4Cl-P), Na2S2O4/NaHCO3 extractable P (BD-P), and HCl extractable P (HCl-P) into NaOH extractable P (NaOH-rP) and residual P (Res-P) in sediment, thereby leading to the reduction of mobile P (sum of NH4Cl-P and BD-P) in sediment. Content of bioavailable P (BAP) including water soluble P (WSP), readily desorbable P (RDP), iron oxide paper strip extractable P (FeO-P), and anion resin extractable P (Resin-P) in sediment also declined following addition of ZrMZ. Control of P release from sediment by ZrMZ could be due to reduction of P in pore water and immobilization of P in sediment. Results of this work indicate that ZrMZ is very promising for controlling P release from sediments in heavily polluted rivers.

[Adsorption Behavior of Phosphate from Water on Zirconium-loaded Granular Zeolite-amended Sediment].

In this study, a zirconium-loaded granular zeolite (ZrGZ) was prepared, characterized and used as a sediment amendment to control internal phosphorus (P) loading in water samples from a heavily polluted river. The adsorption characteristics of phosphate on ZrGZ-amended sediment were investigated using batch experiments, and the stability of P in phosphate-adsorbed ZrGZ was evaluated using a sequential chemical extraction method. Results showed that the Langmuir isotherm model was more suitable for describing the equilibrium adsorption data of phosphate on ZrGZ-amended sediment than the Freundlich and Dubinin-Radushkevich isotherm models. The adsorption process of phosphate on ZrGZ-amended sediment could be well described by the pseudo-second-order and Elovich kinetic models, and both film and intra-particle diffusion controlled the adsorption rate during the gradual adsorption stage. The coexistence of SO42- and HCO3- inhibited the adsorption of phosphate on ZrGZ-amended sediment, while coexisting Na+, K+, Mg2+ and Ca2+ enhanced the phosphate adsorption, and this promoting effect decreased in the order of Ca2+ > Mg2+ > Na+/K+. The ZrGZ-amended sediment exhibited a higher phosphate adsorption capacity than the unamended sediment, and the maximum phosphate adsorption capacity derived from the Langmuir isotherm model was found to be 336 mg·kg-1, which was higher than that for the unamended sediment (215 mg·kg-1). Sequential tests showed that P in phosphate-adsorbed ZrGZ mainly existed in the form of NaOH-rP and Res-P, which was relatively unreactive. These results indicated that ZrGZ addition enhanced the phosphate adsorption capacity of river sediment, and that ZrGZ was a promising amendment for controlling the release of P from river sediment.

[Adsorption of Phosphate from Aqueous Solutions on Sediments Amended with Magnetite-Modified Zeolite].

Understanding the characteristics of phosphate adsorption onto magnetite-modified zeolite (MZ)-amended sediment is helpful for knowing the exchange behavior and process of phosphorus at the interface between the overlying water and MZ-amended sediment. Furthermore, it is helpful for the application of MZ as an amendment to control phosphorus release from sediment. To achieve this goal, the adsorption of phosphate on unamended and MZ-amended sediments was comparatively investigated using a series of batch experiments, and the fractionation of phosphorus in the phosphate-adsorbed MZ was studied using a sequential extraction process. The kinetic data of phosphate adsorption onto unamended and MZ-amended sediments were more suitably fitted to the Elovich model than to the pseudo-first-order and pseudo-second-order models. The equilibrium adsorption data of phosphate adsorption onto the unamended and MZ-amended sediments were well described by the Langmuir, Freundlich, and Dubinin-Radushkevic isotherm model. The phosphate adsorption performance of the unamended and MZ-amended sediments decreased with increasing solution pH from 4 to 11. The presence of cations, such as K+, Mg2+, and Ca2+, enhanced the adsorption of phosphate on the unamended and MZ-amended sediments, and the promoting effect decreased in the order of Ca2+ > Mg2+ > K+, whereas the presence of HCO3- inhibited the adsorption of phosphate. The mechanisms for phosphate adsorption onto the unamended and MZ-amended sediments involved electrostatic attraction and ligand exchange, while the mechanism for the adsorption of phosphate on MZ in the amended sediment involved ligand exchange. The sequential extraction analysis of phosphate-adsorbed MZ showed that 49.4% of phosphorus in MZ existed in the mobile form (NH4Cl-P, BD-P, and NaOH-nrP), which could be easily released from MZ. Therefore, the used MZ should be recovered from sediment using external magnetic fields after its application. The results of this study indicated that MZ is a promising sediment amendment for the control of internal loading in rivers.