Zhifei Dai

Polyoxometalate-Based Organic-Inorganic Hybrids as Antitumor Drugs

Polyoxometalates (POMs) have shown encouraging antitumor activity. However, their cytotoxicity in normal cells and unspecific interactions with biomolecules are two major obstacles that impede the practical applications of POMs in clinical cancer treatment. Derivatization of POMs with more biocompatible organic ligands is expected to cause a synergetic effect and achieve improved bioactivity and biospecificity. Herein, the synthesis of an amphiphilic organic-inorganic hybrid is reported by grafting a long-chain organoalkoxysilane lipid onto a POM. The amphiphilic POM hybrid could spontaneously assemble into the vesicles and exhibits enhanced antitumor activity for human colorectal cancer cell lines (HT29) compared to that of parent POMs. This detailed study reveals that the amphiphilic nature of POM hybrids enables the as-formed vesicles to easily bind to the cell membranes and then be uptaken by the cells, thus leading to a substantial increase in antitumor activity. Such prominent antitumor action is mostly accomplished via cell apoptosis, which ultimately results in cell death. Our finding demonstrates that novel POM hybrids-based drugs with increased bioactivity could be obtained by decorating POMs with selective organic ligands.

One-pot construction of doxorubicin conjugated magnetic silica nanoparticles

Doxorubicin (DOX) conjugated magnetic silica nanoparticles (DOX–Fe3O4–SiO2) are successfully fabricated using a new one-pot method without need for the process of inconvenient multistep synthesis in advance, based on the condensation of DOX and the silica precursor 3-isocyanatopropyltriethoxysilane (ICPTES), followed by the spontaneous formation of a silica coating onto the surface of Fe3O4nanoparticlesvia sol–gel polymerization of triethoxysilane. Mass spectroscopy provides evidence that doxorubicin is conjugated to ICPTES via a urea bond (–NHCONH–) via the reaction of the amino groups of DOX with the isocyanate group (–NCO) of ICPTES in water. The obtained magnetic nanoparticles are well dispersed. Their mean diameter is about 66.9 nm with a narrow size distribution. The conjugated DOX–SiO2–Fe3O4nanoparticles exhibited a higher loading efficiency of 60.5 ± 3.7% and a more sustained release profile than SiO2nanoparticles containing physically-entrapped DOX. It is anticipated that fine-tuning of other drugs or bioactive molecules containing –NH2groups to Fe3O4/SiO2nanoparticles would foster innovative avenues for the development of smart drug delivery and controlled release systems.

Iron/dextran sulfate multilayered microcapsules for controlled release of 10-hydroxycamptothecin.

Stable 10-hydroxycamptothecin (HCPT) microcrystals with a length of about 5-10μm and a ζ-potential of -38.5mV were produced by pH-induced reprecipitation in presence of a stabilizer hydroxypropylmethylcellulose. Sequential layer growth was achieved by the layer-by-layer (LbL) assembly of Fe(3+) and dextran sulfate (DS) on the surface of HCPT microcrystals via both electrostatic interaction and chemical complexation process. The satisfactory drug loading content (67.2±0.82%) as well as high encapsulation efficiency (60.56±0.82%) for four bilayers of Fe(3+)/DS coating was achieved. Both in vitro and in vivo release study revealed that the release time increased as the number of deposited Fe(3+)/DS bilayers increased. These results indicated that such iron-polysaccharide multilayered microcapsules can be a promising approach for the construction of an effective controlled release delivery system of HCPT as well as other drugs with potential cytotoxicity or short half-life time.

Improved biocompatibility of thrombo-resistant iron-polysaccharides multilayer coatings on Nitinols

Biocompatibility of two multilayer coatings of (Fe3+/Hep)10 and (Fe3+/DS/Fe3+/Hep)5 was comparatively analyzed with respect to protein adsorption, leukocyte adhesion and cell-material interaction. Both of them showed significantly high albumin-to-fibrinogen adsorption ratio, suggesting good biocompatibility. Furthermore, the (Fe3+/DS/Fe3+/Hep)5 coating was found to exhibit the lowest non-specific protein adsorption due to the incorporation of dextran sulfate. Compared with uncoated Nitinol surfaces, iron-polysaccharide multilayer coating presented no deformation of leukocytes, indicating no signs of inflammatory reactions. Cell growth, cell adhesion and cell metabolic activity were all in good condition, verifying both (Fe3+/Hep)10 and (Fe3+/DS/Fe3+/Hep)5 coatings had good cytocompatibility. Therefore, iron-polysaccharides multilayer coatings had greatly improved the biocompatibility of Nitinols.

A two-step pH-dependent liquid–liquid extraction combined with HPLC-fluorescence method for the determination of 10-hydroxycamptothecin in mouse liver tissue

Context: Liquid–liquid extraction (LLE) shows high efficiency in the plasma sample preparation. However, this extraction method is not optimal for the biological samples containing complex organic interferences, such as liver and brain tissues. Some plant secondary metabolites can be converted between water-insoluble and water-soluble forms by pH adjustment. Objective: A two-step pH-dependent LLE method was introduced in this study to eliminate both water-soluble and lipidic interferences using the properties of pH-dependent interconvertible forms of analytes during sample preparation. A sensitive and reliable method using a reverse-phase HPLC coupled with a fluorescence detector was developed and validated. Materials and methods: 10-Hydroxycamptothecin (HCPT) with internal standard camptothecin and liver tissues were used as model compounds and biological samples. The lactone form of HCPT was converted to the water-soluble carboxylate form under moderate alkaline conditions, and the water-insoluble interferences were extracted with a nonpolar solvent. Afterward, the water-insoluble lactone form of HCPT was regenerated by acidification and then extracted using an organic solvent in a second LLE step. Results: The calibration curve was linear (r2 > 0.999) for HCPT concentrations ranging from 2.5 to 160u2009ng/mL. The mean recoveries of HCPT were 114.94u2009±u20093.98, 104.30u2009±u20092.44 and 95.90u2009±u20091.40% (nu2009=u20096) at concentrations of 2.5, 10 and 80u2009ng/mL, respectively. The stability determination data showed that no significant degradation occurred under the experimental conditions. This method was successfully applied to liver tissue distribution study of HCPT in mice. Discussion and conclusion: This two-step LLE can be applied to distribution studies of compounds with pH-dependent interconvertible forms in other biological matrices.