Conghui Yuan

Gold@Polymer Nanostructures with Tunable Permeability Shells for Selective Catalysis

National Natural Science Foundation of China [50873082, 50903067]; Scientific and Technical Project of Fujian Province of China [2009J1009, 2010H6021]

Orthogonally Functionalized Nanoscale Micelles for Active Targeted Codelivery of Methotrexate and Mitomycin C with Synergistic Anticancer Effect

The design of nanoscale drug delivery systems for the targeted codelivery of multiple therapeutic drugs still remains a formidable challenge (ACS Nano, 2013, 7, 9558-9570; ACS Nano, 2013, 7, 9518-9525). In this article, both mitomycin C (MMC) and methotrexate (MTX) loaded DSPE-PEG micelles (MTX-M-MMC) were prepared by self-assembly using the dialysis technique, in which MMC-soybean phosphatidylcholine complex (drug-phospholipid complex) was encapsulated within MTX-functionalized DSPE-PEG micelles. MTX-M-MMC could coordinate an early phase active targeting effect with a late-phase synergistic anticancer effect and enable a multiple-responsive controlled release of both drugs (MMC was released in a pH-dependent pattern, while MTX was released in a protease-dependent pattern). Furthermore, MTX-M-MMC could codeliver both drugs to significantly enhance the cellular uptake, intracellular delivery, cytotoxicity, and apoptosis in vitro and improve the tumor accumulation and penetration and anticancer effect in vivo compared with either both free drugs treatment or individual free drug treatment. To our knowledge, this work provided the first example of the systemically administrated, orthogonally functionalized, and self-assisted nanoscale micelles for targeted combination cancer chemotherapy. The highly convergent therapeutic strategy opened the door to more simplified, efficient, and flexible nanoscale drug delivery systems.

A Simple Dual-pH Responsive Prodrug-Based Polymeric Micelles for Drug Delivery

To precisely deliver drug molecules at a targeted site and in a controllable manner, there has been great interest in designing a synergistical drug delivery system that can achieve both surface charge-conversion and controlled release of a drug in response to different stimuli. Here we outline a simple method to construct an intelligent drug carrier, which can respond to two different pH values, therefore achieving charge conversion and chemical-bond-cleavage-induced drug release in a stepwise fashion. This drug carrier comes from the self-assembly of a block copolymer-DOX conjugate synthesized through a Schiff base reaction between poly(2-(diisopropylamino)ethyl methacrylate-b-poly(4-formylphenyl methacrylate-co-polyethylene glycol monomethyl ether methacrylate) (PDPA-b-P(FPMA-co-OEGMA)) and DOX. The surface charge of the BCP-DOX micelles reversed from negative to positive when encountering a weakly acidic environment due to the protonation of PDPA segments. In vitro cellular uptake measurement shows that the cellular uptake and internalization of the BCP-DOX micelles can be significantly enhanced at pH ∼ 6.5. Moreover, this drug carrier exhibits a pH-dependent drug release owing to the cleavage of the imine bond at pH < 5.5. With this dual-pH responsive feature, these micelles may have the ability to precisely deliver DOX to the cancer cells.

Modification of epoxy resin through the self-assembly of a surfactant-like multi-element flame retardant

In order to develop a multi-element, synergistic, flame-retardant system, the combination of DOPO, POM and POSS was achieved using the classical Kabachnik–Fields reaction. The as-designed POSS-bisDOPO was characterized by FT-IR, 1H NMR, 13C NMR, 31P NMR, 2D NMR, and MS. POSS-bisDOPO was introduced into epoxy resins to obtain flame-retardant materials. The LOI value can reach 34.5% when the content of POSS-bisDOPO is 20 wt%. The TGA results showed that the char yield was significantly improved in cured POSS-bisDOPO/EP. The ATR-FTIR results, optical images and SEM analyses indicated that the residual char had a compact and coherent appearance in the inner layer, while the outer structure was intumescent and multi-porous. Therefore, by isolating heat and oxygen more efficiently, the char played an important role in improving the thermal stability and flame retardancy of cured POSS-bisDOPO/EP. The three-point bending test results showed that the mechanical strength of POSS-bisDOPO/EP was higher than those of pure EP and POSS–NH2/EP due to the outstanding reinforcement effect of the unique nanostructure of POSS-bisDOPO assembled in the EP matrix. These data indicated that POSS-bisDOPO not only obviously enhances the flame retardancy, but also improves the mechanical properties of epoxy resins.

Surface charge generation in nanogels for activated cellular uptake at tumor-relevant pH

Nanocarriers that can be effectively transported across cellular membranes have potential in a variety of biomedical applications. Among these, materials that are capable of changing their surface properties and thus gain entry into a cell, in response to a specific tissue environment, are of particular interest. In this manuscript we report a facile route to prepare nanogels, which generate surface charge with pH as stimulus. This is achieved by designing a polymeric nanogel containing 2-diisopropylamino (DPA) moieties. The choice of DPA nanogel is based on its pKb, which causes this functional group to be rapidly protonated upon change in pH. It is noteworthy that the pH change at which the surface charge is generated in the nanogel corresponds to the slightly acidic conditions observed in the extracellular environment of solid tumor. We show that the pH at which the charge is generated, i.e. the isoelectric point (pI) of the nanogel, can be adjusted by varying the percentage of DPA units in the nanogel, its preparation process and crosslinking density. Intracellular delivery of these nanogels was greatly enhanced in an acidic pH environment due to the surface charge generation. This study demonstrates the versatile nature of the nanogels to introduce specific functionalities with relative ease to achieve desired functional behavior.

CuO based inorganic-organic hybrid nanowires: a new type of highly sensitive humidity sensor

The organic surfactant template method has been widely used for the preparation of CuO nanorods, nanotubes and nanowires. However, the surfactants in this system have no effect on the properties of the final products because they are flushed away. In this work, we used this method to synthesize a novel type of inorganic-organic hybrid nanowire via the hybridization between CuO and amphiphilic oligomer octadecyl, polyethylene glycol di-butenetrioate (O-B-EG-B). Here O-B-EG-B, as a structure director, was not flushed away but remained in the prepared hybrid nanowires because it was bound around CuO or entrapped in interior CuO. The hybrid nanowires showed CuO cores and P(O-B-EG-B) shells when the concentration of O-B-EG-B was 0.4 mg ml(-1), but exhibited P(O-B-EG-B) cores and CuO shells when the concentration of O-B-EG-B was 4.0 mg ml(-1). We found that the hybrid nanowires with P(O-B-EG-B) cores and CuO shells could sense a slight change in the relative humidity (RH) and respond by rapidly changing their conductivity. The resistance changed by about two orders of magnitude within the humidity range from 5% to 83.8%. Moreover, a humidity sensor based on this type of nanowire not only showed long-term stability but also exhibited excellent reversibility to moisture changes in air.

Novel methotrexate prodrug-targeted drug delivery system based on PEG–lipid–PLA hybrid nanoparticles for enhanced anticancer efficacy and reduced toxicity of mitomycin C

In the present study we have investigated novel MTX prodrug-targeted and MMC-loaded PLA-lipid-PEG hybrid NPs. These employ a double emulsion solvent evaporation method for the introduction of an anticancer drugs moiety of the MMC-soybean phosphatidylcholine complex or DSPE-PEG-MTX, in which the MTX prodrug can be exploited as a targeting ligand. The prepared drug delivery systems present a spherical shape, a small particle size (219.6 ± 2.1 nm) with narrow particle size distribution, high MMC encapsulation efficiency (90.5 ± 3.0%) and a sustained and pH-controlled MMC release. The advantage of the new drug delivery systems is that the two-anticancer drug moiety can coordinate the early-phase targeting effect with the later-phase anticancer effect. In vivo pharmacokinetics, following intravenous administration of the drug delivery systems, indicates a prolonged systemic circulation time of MMC. More importantly, the drug delivery systems exhibited a significant accumulation of MMC in the nuclei as the site of MMC action, which was indicative of the enhancement of anticancer activity. Such a design of drug delivery systems may open up a new horizon for targeted delivery and sustained and controlled release of MMC.

Composite supramolecular nanoassemblies with independent stimulus sensitivities

Nanoscale assemblies with stimuli-sensitive features have attracted significant attention due to implications in a variety of areas ranging from materials to biology. Recently, there have been excellent developments in obtaining nanoscale structures that are concurrently sensitive to multiple stimuli. Such nanostructures are primarily focused on a single nanostructure containing an appropriate combination of functional groups within the nanostructure. In this work, we outline a simple approach to bring together two disparate supramolecular assemblies that exhibit very different stimuli-sensitive characteristics. These composite nanostructures comprise a block copolymer micelle core and nanogel shell, both of which can preserve their respective morphology and stimulus sensitivities. The block copolymer is based on poly(2-(diisopropylamino)ethylmethacrylate-b-2-aminoethylmethacrylate hydrochloride), which contains a pH-sensitive hydrophobic block. Similarly, the redox-sensitive nanogel is derived from a poly(oligoethyleneglycolmonomethylethermethacrylate-co-glycidylmethacrylate-co-pyridyldisulfide ethylmethacrylate) based random copolymer. In addition to the independent pH-response of the micellar core and redox-sensitivity of the nanogel shell in the composite nanostructures, the synergy between the micelles and the nanogels have been demonstrated through a robust charge generation in the nanogels during the disassembly of the micelles. The supramolecular assembly and disassembly have been characterized using transmission electron microscopy, dynamic light scattering, zeta potential measurements, fluorescence spectroscopy and cellular uptake.

Colloidosomes constructed by the seamless connection of nanoparticles: a mobile and recyclable strategy to intelligent capsules

Colloidosomes constructed by the self-assembly of nanoparticles (NPs) on liquid–liquid interfaces have been demonstrated to be useful in many fields. However, the interspaces between NPs on the surface of colloidosomes barricade their application in small molecule encapsulation. Herein, fabrication of a new type of colloidosome built by the seamless connection of NPs via simply heating and quenching a type of core–shell structured NPs (CSNPs) aqueous system using oil as a template, is presented. These colloidosomes have a hollow structure and exhibit efficient small molecule encapsulation. More importantly, the colloidosomes can dissociate into single NPs and release the small target molecules encapsulated in interior of the colloidosomes at a temperature higher than the melting point of the CSNP shell. It is also shown that the dissociation temperature of colloidosomes can be controlled by simply adjusting the length of the PEG chains in the CSNP shell, which implies that these intelligent capsules have attractive application prospects in controlled drug release.

Synthesis of walnut-like hierarchical structure with superhydrophobic and conductive properties

Walnut-like structures made up of a polyaniline (PANI) nanofiber network and polystyrene (PS) microspheres are successfully fabricated by a novel approach, “competitive adsorption–restricted polymerization”. In the reaction system, PS microspheres are simultaneously encapsulated by cationic surfactant and aniline hydrochloride. Just this cationic surfactant molecule affects the nucleation model and second growth of PANI via electrostatic interactions and steric hindrance, which accounts for the formation of a PANI nanofiber network coating on the PS surface. The size, ordering and amount of PANI nanofibers on the three-dimensional surface can be particularly controlled by altering a variety of synthetic conditions, such as the amount of cationic surfactant, temperature and concentration. A superhydrophobic and conductive surface is obtained by drop-casting a suspension of these walnut-like PS/PANI particles onto a substrate.