Targeting epithelial-mesenchymal transition: Metal organic network nano-complexes for preventing tumor metastasis.

Tumor metastasis is the leading cause of death in cancer patients, and epithelial-mesenchymal transition (EMT) is an essential step in tumor metastasis. Unfortunately, during the chemotherapy, EMT could be induced under the selective pressure of clinical cytotoxic drugs. Here, to solve this problem, we have synthesized multi-functional epigallocatechin gallate/iron nano-complexes (EIN) as a versatile coating material to improve conventional therapies. In vitro studies showed that this strategy could eliminate EMT-type cancer cells. Mechanism studies also revealed that EIN was able to down-regulate the downstream expression of metastasis-associated factors, decrease the migration ability of cancer cells and prevent cancer cells from gaining drug resistance. In vivo investigation revealed that EIN had superior ability to enhance the therapeutic effect of conventional nanomedicines and inhibit the EMT process. Our study indicates the promising use of EIN to make up for the deficiencies of chemotherapy may provide insights into systematic cancer therapy to overcome tumor metastasis and drug resistance.

Viscosity enhanced release (VER) effect in nanoporous drug delivery systems: phenomenon and mechanism.

High viscosity is important for normal intracellular homeostasis. In this study, nanoporous drug delivery systems (DDSs), including mesoporous silica nanoparticles (MSNs) and layer by layer (LBL) microcapsules, with a viscosity enhanced release (VER) effect were designed and prepared, and their drug release behaviors in a sticky environment with a high viscosity were investigated using rhodamine B, methylene blue and doxorubicin (DOX) as model drugs. The results showed that the drug release rate from DDSs in a biomimetic high viscosity solution was 7 to 8 times higher than that in water. A semipermeable membrane model was used to explain the VER effect. The results indicate that the existence of macromolecules in the release medium caused a VER effect. The VER effect found in this study will provide a new concept to guide the design of DDSs in a high viscosity environment in vivo.

Supermolecular theranostic capsules for pH-sensitive magnetic resonance imaging and multi-responsive drug delivery.

Magnetite (Fe3O4) microcapsules prepared by layer-by-layer self-assembly are investigated as multi-functional magnetic resonance imaging contrast agents and drug carriers. They are produced by host-guest interactions and Coulombic force from different supramolecular polymers. Drug molecules are released controllably from the microcapsules by non-invasive ultra-violet light induced photo-isomerization of the azobenzene molecule and pH sensitive Schiff's base. In addition, by encapsulation of the superparamagnetic iron oxide nanoparticles (SPION) in the nearby layers, magnetic field targeting and MRI contrast are achieved. Under tumor-like acidic conditions (pH = 5.6), the r2 relaxivity of the microcapsules is 126 mM-1 s-1 which is 37% higher than that in a neutral environment (92 mM-1 s-1). As a result of the low pH enhanced MRI contrast agent, the tumor structure can be observed clearly in vivo confirming the high efficacy as a negative MRI agent in T2-weighted imaging. The materials as combined carriers have great potential in clinical applications as drug delivery agents and contrast agents in MRI.

Study on the Langmuir aggregation of sodium octanesulfonate on human serum albumin.

The microphase adsorption-spectral correction (MPASC) technique was described and applied to the study of the interactions of sodium octanesulfonate (SOS) with human serum albumin (HSA). The aggregation SOS obeys the Langmuir monolayer adsorption. The results show the adsorption ratio of sodium octanesulfonate to HSA is SOS:HSA=18:1.The adsorption constant is K(SOS-HSA)=4.03 × 10(2). The detection limit is 0.036µmol/L. FT-IR spectra proved the binding changed the conformation of HSA.

Cationic fluorine-containing amphiphilic graft copolymers as DNA carriers.

A series of cationic fluorine-containing amphiphilic graft copolymers P(HFMA-St-MOTAC)-g-PEG comprising poly(hexafluorobutyl methacrylate) (PHFMA) poly(methacryl oxyethyl trimethylammonium chloride) (PMOTAC) polystyrene (PSt) backbones and poly(ethylene glycol) (PEG) side chains are synthesized as a type of non-viral gene vector. The copolymers self-assemble into spherical micelles in the aqueous media and turbidity and cytotoxicity measurements show that those micelles have excellent dispersive stability and low cytotoxicity. The interactions between the copolymers and calf-thymus DNA are studied by fluorescence spectroscopy and viscosity. The former discloses electrostatic interaction, hydrophobic interaction, and hydrogen bonding in the copolymer/DNA system, whereas the latter indicates that these graft copolymers can bind DNA via the electrostatic and classical intercalation modes. The DNA-binding capacity determined by the gel retardation assay and UV-visible spectrophotometry shows that the copolymers have good binding capacity to DNA and a high charge density or HFMA content in the copolymers bode well for DNA-binding. Transmission electron microscopy, photon correlation spectroscopy, and zeta potential data reveal that stable colloidal complexes (particles) can form easily between the copolymer micelles and DNA. Our results suggest that the copolymers are a promising non-viral vector in a gene delivery system.