Cellular internalization and in vivo tracking of thermosensitive luminescent micelles based on luminescent lanthanide chelate.

An amphiphilic tris(dibenzoylmethanato)europium(III) (Eu(DBM)(3)) coordinated P(MMA-co-EIPPMMA)-co-P(NIPAAm-co-NDAPM) copolymer was synthesized, which exhibited good biocompatibility and emitted strong red luminescence (MMA, methyl methacrylate; EIPPMMA, 4-(1-ethyl-1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenyl methacrylate; NIPAAm, N-isopropylacrylamide; NDAPM, (N-(3-dimethylamino)propyl)methacrylamide). The copolymer could self-assemble into micelles of size around 260 nm, and the micelles were thermosensitive at around body temperature. The drug-loaded micelles showed thermosensitive controlled drug release, and the paclitaxel loaded micelles were capable of being internalized into the tumor cells (A549) and exhibited obvious inhibition to the growth of A549 cells.

Degradable nanogels as a nanoreactor for growing silica colloids.

Degradable nanogels with cleavable disulfide bonds were designed and used as a catalytic template, providing an alkali microenvironment. Well-defined hybrid silica colloids could be obtained by hydrolyzing tetraethyl orthosilicate (TEOS) in the nanogels. The size of silica colloids was found to be dependent on the size of the nanogels.

Targeted gene delivery mediated by folate-polyethylenimine-block-poly(ethylene glycol) with receptor selectivity.

The folate receptor (FR) is a tumor marker overexpressed in large numbers of cancer cells. Folic acid has high affinity to the FR and retains its binding affinity upon derivatization via its gamma-carboxyl. Therefore, in this article, folate-polyethylenimine-block-poly(ethylene glycol) (FOL-PEI-b-PEG) was designed for specific receptor targeted gene delivery.

Modular Synthesis of Thermosensitive P(NIPAAm-co-HEMA)/β-CD Based Hydrogels via Click Chemistry.

Two kinds of representative polymers, poly(N-isopropylacrylamide) (PNIPAAm) and β-cyclodextrin (β-CD) were selected and modified with azide and alkyne fucntional groups, respectively. When the solutions of these two modified polymers were mixed together, a cross-linking reaction, a type of Huisgen's 1,3-dipolar azide-alkyne cycloaddition, occurred in the presence of Cu(I) catalyst. The strategy described here provides several advantages for the hydrogel formation including mild reaction conditions and controllable gelation rate.

Novel thermosensitive hydrogel injection inhibits post-infarct ventricle remodelling.

Aims: Myocardial infarction (MI) remains the commonest cause of cardiac-related death throughout the world. Adverse cardiac remodelling and progressive heart failure after MI are associated with excessive and continuous damage of the extracellular matrix (ECM). In this study, we hypothesized that implantation of hydrogel into infarcted myocardium could replace the damaged ECM, thicken the infarcted wall, and inhibit cardiac remodelling.

Galactosylated fluorescent labeled micelles as a liver targeting drug carrier.

Galactosylated and fluorescein isothiocyanate (FITC) labeled polycaprolactone-g-dextran (Gal-PCL-g-Dex-FITC) polymers were synthesized. The grafted polymers can self-assemble into stable micelles in aqueous medium and in serum. Transmission electron microscopy (TEM) images showed that the self-assembled micelles were regularly spherical in shape.

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH-sensitive drug release property.

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH sensitivity were developed for oral delivery of protein drugs, using bovine serum albumin (BSA) as a model drug. The composite drug-loaded microparticles with a mean particle size less than 200mum were prepared by a convenient shredding method. Since the microparticles were formed by tripolyphosphate cross-linking, electrostatic complexation by alginate and/or pectin, as well as ionotropic gelation with calcium ions, the microparticles exhibited an improved pH-sensitive drug release property.

Protamine sulfate/poly(L-aspartic acid) polyionic complexes self-assembled via electrostatic attractions for combined delivery of drug and gene.

In this study, a series of self-assembled polyionic complexes (PICs) were prepared via electrostatic attraction between protamine sulfate (PS) and poly(L-aspartic acid) (PASP) or doxorubicin (DOX)-conjugated PASP (DOX-PASP). The size of the PICs measured by Nano-ZS ZEN3600 was around 200-300 nm at different weight ratios of PS/PASP. Transmission electron microscopy (TEM) showed that PS/PASP PICs displayed a regular spherical shape and no aggregation was observed.

Study on novel hydrogels based on thermosensitive PNIPAAm with pH sensitive PDMAEMA grafts.

A series of novel hydrogels based on poly(N-isopropylacrylamide) (PNIPAAm) with pendant poly(N-(2-(dimethylamino) ethyl)-methacrylamide) (PDMAEMA) grafts were designed and synthesized. The influence of the pendant PDMAEMA grafts on the properties of the resulted hydrogels was examined in terms of morphology observed by scanning electron microscopy (SEM), thermal property characterized by differential scanning calorimetry (DSC) and shrinking/swelling kinetics upon external temperature changes. In comparison with the conventional PNIPAAm hydrogels, resulting hydrogels presented favorable pH sensitivity as well as improved thermosensitive properties, including enlarged water containing capability at room temperature and faster shrinking/swelling rate upon heating.

The tuned-morphology studies of the complexes between poly(N-isopropylacrylamide)-b-poly(vinylpyridine) and poly(N-isopropylacrylamide-co-hydroxylethyl methacrylate)-b-poly(vinylphenol).

Poly(N-isopropylacrylamide)-b-poly(vinylpyridine) (PNIPAAm-b-PVP) and poly(N-isopropylacrylamide-co-hydroxylethyl methacrylate)-b-poly(vinylphenol) (P(NIPAAm-co-HEMA)-b-PVPhol) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Above two copolymers could form complex in pure water and in DMF/water environment with the DMF content lower than 40% by hydrogen bondings. The morphologies of the complex were investigated by transmission electron microscope (TEM).

Dendrimer/DNA complexes encapsulated functional biodegradable polymer for substrate-mediated gene delivery.

Background: To overcome the extracellular barriers in gene delivery and direct gene delivery to target tissues, substrate-mediated transfection, which sustains the release of naked DNA or vector/DNA complexes, and also supports cell growth, has been developed.

Methods: In the present study, polyamidoamine (PAMAM) dendrimer/DNA complexes encapsulated functional biodegradable polymer films for substrate-mediated gene delivery were prepared. To maintain the activity of DNA during dehydration, the dendrimer/DNA complexes were encapsulated in a water soluble polymer, poly alpha,beta-[N-(2-hydroxyethyl)-(L)-aspartamide], and then deposited on or sandwiched in functional polymer films with a fast degradation rate to mediate gene transfection.

Direct observation of time and temperature dependent transition from spherical micelles to vesicles.

An interesting transition from spherical micelles to vesicles, which was time and temperature dependent, was observed for the first time; it is tentatively attributed to the thermal hysteresis of temperature-responsive poly(N-isopropylacrylamide).

Supramolecular structure and properties of high strength regenerated cellulose films.

Water-swollen cellulose films prepared from LiOH/urea solution were uniaxially drawn to investigate the effect of orientation on their supramolecular structure and properties. Their structures and properties were investigated with X-ray diffraction, atomic force microscopy and tensile testing. The results revealed that the drawing process led to substantial reorientation of the cellulose molecular chains, resulting in a significant improvement of their mechanical properties and water-resistance.

A nanosized, thermo-sensitive drug carrier: self-assembled Fe(3)O(4)-OA-g-P(OA-co-NIPAAm) magnetomicelles.

Novel thermo-sensitive magnetomicelles that consist of a magnetic core, Fe(3)O(4)-oleic acid (Fe(3)O(4)-OA), and an amphiphilic surface layer of thermo-sensitive poly(oleic acid-co-N-isopropylacrylamide) P(OA-co-NIPAAm) co-polymer were prepared. Fe(3)O(4) magnetic cores functionalized with double bonds of oleic acid were prepared by suspension-oxidation reaction. Subsequently, by the co-polymerization of hydrophilic NIPAAm, hydrophobic OA and the Fe(3)O(4)-OA magnetic core, the thermo-sensitive amphiphilic polymers (P(OA-co-NIPAAm)) were grafted to obtain Fe(3)O(4)-OA-g-P(OA-co-NIPAAm) nanoparticles.

The influence of RGD addition on the gene transfer characteristics of disulfide-containing polyethyleneimine/DNA complexes.

Arginine-glycine-aspartic acid (RGD) ligand is often chemically attached to polycation vector to improve the transfection efficiency. However, the chemical reaction may reduce or even inactivate the biological activities of peptides. In order to retain the targeting ability and biological activities, the RGD peptide was noncovalently introduced into polycations as gene delivery systems.

Low molecular weight polyethylenimine grafted N-maleated chitosan for gene delivery: properties and in vitro transfection studies.

To develop chitosan-based efficient gene vectors, chitosans with different molecular weights were chemically modified with low molecular weight polyethylenimine. The molecular weight and composition of polyethylenimine grafted N-maleated chitosan (NMC-g-PEI) copolymers were characterized using gel permeation chromatography (GPC) and (1)H NMR, respectively. Agarose gel electrophoresis assay showed that NMC-g-PEI had good binding ability with DNA, and the particle size of the NMC-g-PEI/DNA complexes was 200-400 nm, as determined by a Zeta sizer.

Fabrication of supramolecular hydrogels for drug delivery and stem cell encapsulation.

Supramolecular hydrogels self-assembled by alpha-cyclodextrin and methoxypolyethylene glycol-poly(caprolactone)-(dodecanedioic acid)-poly(caprolactone)-methoxypolyethylene glycol (MPEG-PCL-MPEG) triblock polymers were prepared and characterized in vitro and in vivo. The sustained release of dextran-fluorescein isothiocyanate (FITC) from the hydrogels lasted for more than 1 month, which indicated that the hydrogels were promising for controlled drug delivery. ECV304 cells and marrow mesenchymal stem cells (MSC) were encapsulated and cultured in the hydrogels, during which the morphologies of the cells could be kept.

Functionalized amphiphilic hyperbranched polymers for targeted drug delivery.

Amphiphilic hyperbranched core-shell polymers with folate moieties as the targeting groups were synthesized and characterized. The core of the amphiphilic polymers was hyperbranched aliphatic polyester Boltorn H40. The inner part and the outer shell of the amphiphilic polymers were composed of hydrophobic poly(epsilon-caprolactone) segments and hydrophilic poly(ethylene glycol) (PEG) segments, respectively.

Homogeneous quaternization of cellulose in NaOH/urea aqueous solutions as gene carriers.

Quaternized celluloses (QCs) were homogeneously synthesized by reacting cellulose with 3-chloro-2-hydroxypropyltrimethylammonium chloride (CHPTAC) in NaOH/urea aqueous solutions. The structure and solution properties of the QCs were characterized by using elemental analysis, FTIR, (13)C NMR, SEC-LLS, viscometer, and zeta-potential measurement. The results revealed that water-soluble QCs, with a degree of substitution (DS) value of 0.

Novel thermoresponsive nonviral gene vector: P(NIPAAm-co-NDAPM)-b-PEI with adjustable gene transfection efficiency.

A thermoresponsive cationic copolymer, poly( N-isopropylacrylamide- co- N-(3-(dimethylamino)propyl)methacrylamide)- b-polyethyleneimine (P(NIPAAm- co-NDAPM)- b-PEI), was designed and synthesized as a potential nonviral gene vector. The lower critical solution temperature (LCST) of P(NIPAAm- co-NDAPM)- b-PEI in water measured by UV-vis spectroscopy was 38 degrees C. P(NIPAAm- co-NDAPM)- b-PEI as the gene vector was evaluated in terms of cytotoxicity, buffer capability determined by acid-base titration, DNA binding capability characterized by agarose gel electrophoresis and particle size analysis, and in vitro gene transfection.

Thermosensitive P(NIPAAm-co-PAAc-co-HEMA) nanogels conjugated with transferrin for tumor cell targeting delivery.

Multifunctional and thermosensitive poly(N-isopropylacrylamide-co-propyl acrylic acid-co-hydroxyethyl methacrylate) (P(NIPAAm-co-PAAc-co-HEMA)) nanogels were prepared by miniemulsion polymerization. The mean sizes of the nanogels measured by dynamic light scattering (DLS) varied from 120 to 400 nm with an increase in temperature. Transmission electron microscopy (TEM) showed that the nanogels displayed well-dispersed spherical morphology.

Polyethyleneimine modified biocompatible poly(N-isopropylacrylamide)-based nanogels for drug delivery.

A series of biocompatible and stimuli-sensitive poly(N-isopropylacrylamide-co-propyl acrylic acid) (P(NIPAAm-co-PAAc)) nanogels were synthesized by emulsion polymerization. In addition, polyethyleneimine (PEI) was further grafted to modify the PNIPAAm-based nanogels. The P(NIPAAm-co-PAAc)-g-PEI nanogels exhibited good thermosensitivity as well as pH sensitivity.

Injection of a novel synthetic hydrogel preserves left ventricle function after myocardial infarction.

Myocardial infarction (MI) and the subsequent heart failure remain one of the leading causes of morbidity and mortality world wide. A number of studies have demonstrated that bioderived materials improve cardiac function after implantation because of their angiogenic potential. In this study, we hypothesized that injection of biomaterials into infarcted myocardium can preserve left ventricular (LV) function through its prevention of paradoxical systolic bulging.

Functionalized thermoresponsive micelles self-assembled from biotin-PEG-b-P(NIPAAm-co-HMAAm)-b-PMMA for tumor cell target.

Novel micelles, comprising hydrophilic PEG shells, hydrophobic PMMA cores, and thermosensitive P(NIPAAm-co-HMAAm) segments were self-assembled from the biotin-PEG-b-P(NIPAAm-co-HMAAm)-b-PMMA triblock copolymer. The thermosensitive micelles exhibited superior stability and showed thermotriggered drug release behavior upon temperature alterations. The fluorescence spectroscopy and confocal microscopy studies confirmed that the self-assembled biotinylated micelles can be specifically and efficiently bonded to cancer cells with the administration of biotin-transferrin, suggesting that the multifunctional micelles have great potential as drug carriers for tumor targeting chemotherapy.