Hongjing Dou

Two-in-one fabrication of Fe3O4/MePEG-PLA composite nanocapsules as a potential ultrasonic/MRI dual contrast agent.

A new method for the fabrication of Fe(3)O(4) nanoparticles enveloped by polymeric nanocapsules is proposed. This method is characterized by combining a double emulsification with the interfacial coprecipitation of iron salts to form Fe(3)O(4)/polymer composite nanocapsules in a single step. To demonstrate the viability of this approach, methoxy poly(ethylene glycol)-poly(lactide) (MePLEG) was chosen as the shell material for Fe(3)O(4)/MePLEG nanocapsules. In addition to the versatility offered for fabricating nanocapsules with different shell materials, the method was found to be convenient for adjusting the magnetite content of the nanocapsules from 0 to 43%. In addition to their confirmed T(2)-weighted magnetic resonance imaging (MRI) enhancement, the resultant composite nanocapsules display much more obvious acoustic responses than MePLEG nanocapsules in an acoustic investigation. Furthermore, the low toxicity of these composite nanocapsules, as confirmed by our study, combined with their magnetic and acoustic properties ensure that these composite nanocapsules have great potential in acting as ultrasonic/MRI dual contrast agents.

Highly fluorescent water soluble CdxZn1−xTe alloyed quantum dots prepared in aqueous solution: one-step synthesis and the alloy effect of Zn

A novel water-soluble CdxZn1−xTe alloyed quantum dot (QD) with glutathione (GSH) as the stabilizer was prepared for the first time through a one-step aqueous route. Due to the positive alloy effect of Zn in CdTe, the as-prepared CdxZn1−xTe alloyed QDs possess broadened band gap, hardened lattice structure and lower defect densities. Accordingly, the size and composition-dependent fluorescent emission wavelength of the resultant CdxZn1−xTe alloyed QDs can be tuned from 470 to 610 nm, and their photoluminescent quantum yield (PL QY) can reach up to 75%. Especially in the wavelength range of 500–590 nm, the overall PL QYs of the as-prepared CdxZn1−xTe QDs were above 50%, which indicates their great predominance in bio-applications. Moreover, a simple tool for quick and ultrasensitive Pb2+ and Hg2+ detection was produced by measuring the relatively PL intensity of GSH-capped CdxZn1−xTe alloyed QDs with a common fluorophotometer, which also shows their promising application on heavy metal ion detection.

Highly-fluorescent alloyed quantum dots of CdSe1−xTex synthesized in paraffin liquid: gradient structure and promising bio-application

By using paraffin liquid and oleic acid as the solvent and ligand, highly-fluorescent red to near-infrared (NIR)-emitting cadmium selenium telluride (CdSe1−xTex) alloyed quantum dots (QDs) with photoluminescence quantum yield (PLQY) up to 70% were successfully prepared. The as-prepared CdSe1−xTex QDs also demonstrated good optical stabilities against the temperature change and photobleaching due to their gradient “CdTe-rich core/CdSe-rich surface” quasi “core/shell” structure, which was confirmed by studying the alloying process of CdSe1−xTex QDs. Moreover, the as-prepared red to NIR CdSe1−xTex QDs were successfully incorporated into the carboxyl capped porous polystyrene (PS) microbeads to fabricate red to NIR-emitting microbeads with low in vitro cytotoxicity, and the biotinylated goat anti-mouse IgG could be specifically coupled to the optical encoded beads via mouse anti-human chorionic gonadotrophin connected to the carboxyl groups on the encoded microbeads successfully, which suggested promising application of CdSe1−xTex QDs in multiplexed bioassays.

Efficient Incorporation of Quantum Dots into Porous Microspheres through a Solvent-Evaporation Approach

Quantum dot (QD)-encoded microspheres play an important role in suspension arrays by acting as supports for various reactions between biomolecules. With regard to QD-encoded microspheres utilized in suspension arrays, three key requirements are controllable size, abundant surface functional groups, and especially excellent fluorescence properties. In this paper, narrowly dispersed poly(styrene-co-divinylbenzene-co-methylacrylic acid) (PSDM) microspheres with specific size, surface carboxyl groups, and porous structures were synthesized by seeded copolymerization. In order to improve the incorporation efficiency of QDs within microspheres, we developed a swelling-evaporation approach in which the swelling process was combined with gradual evaporation of the solvent and thus gradual concentration of QDs in the dispersion solution. This approach was demonstrated to be an efficient method for improving the fluorescence intensity of resultant microspheres compared with the use of swelling alone. Moreover, the porous structure was shown to aid the penetration of QDs into the interiors of the microspheres. Through this approach, microspheres encoded with either single or multiple wavelength-emitting QDs were fabricated effectively. The suspension immunoassays were then founded based on the QD-encoded microspheres, by coating mouse antihuman chorionic gonadotropin as the probe for goat antimouse IgG detection. The positive results determined by Luminex 100 and the low cytotoxicity of the QD-encoded microspheres demonstrated their great potential in suspension arrays.

Triblock terpolymer helices self-assembled under special solvation conditions

We recently reported an accidental discovery that a linear triblock terpolymer, poly(butyl methacrylate)-block-poly(2-cinnamoyloxyethyl methacrylate)-block-poly(tert-butyl acrylate) (B350C160T160, with the subscripts denoting the numbers of repeat units for the different blocks), self-assembled into double, and sometimes triple, helices in three binary solvent mixtures that were marginal for the B350 block, poor for the C160 block, and good for the T160 block. We show in this paper that double helices were formed as a self-assembly product from B350C160T160 in another three solvent mixtures. Also, a triple-stranded superstructure bearing helical sections was prepared from a new BnCmTl sample, which was B240C120T120. In addition, we have replaced some of the cinnamoyl groups of the C120 block with three types of chiral groups. Multi-stranded superstructures bearing helical sections were produced in every case when the solvents met the special solvation conditions. The partial or full hydrolysis of the T160 and T120 blocks of the two terpolymers yielded acrylic acid bearing blocks and represented the largest structural change from the original terpolymers. Interestingly, these polymers formed helices as well. These helices were double-stranded and had regular pitch lengths. These new results suggest that the use of the special solvation conditions may represent a general paradigm for the production of helices from different triblock terpolymers.

Facile fabrication of dextran-based fluorescent nanogels as potential glucose sensors

Glucose-responsive nanogels based on dextran and poly(3-acrylamidophenylboronic acid) (PAAPBA) were fabricated by a facile self-assembly assisted (SAA) strategy. Further introduction of the fluorescent agent 2-[4-(3-hydroxy-4-oxo-4H-chromen-2-yl)phenoxy]ethylacrylamide (3HF-AM) allowed visualization of this glucose sensitivity, thus ensuring their potential use as glucose sensors.

Fluorescent dextran-based nanogels: efficient imaging nanoprobes for adipose-derived stem cells

For the efficient tracking of adipose-derived stem cells (ADSCs), nano-sized probes provide convenient platforms and have many advantages over the induction of reporter genes. Despite their great potential for various applications, investigations on macromolecular nanogels acting as stem cell tracking probes remain limited due to the difficulties encountered with synthesizing macromolecular nanogels with controllable diameters and surface charges. In this report, we describe a self-assembly assisted (SAA) methodology for the efficient preparation of fluorescent dextran-based nanogels as ADSC imaging nanoprobes. Through a three step procedure involving the fabrication of dextran-based nanogels, the conjugation of fluorescent molecules with the nanogels, and the surface modification of the fluorescent nanogels, novel fluorescent nanogels with various diameters ranging from 165 to 241 nm and surface potentials ranging from −10 to 10 mV were fabricated. The feasibility of these nanogels for ADSC imaging applications was also investigated. We demonstrate that negatively charged nanogels provide effective ADSC imaging without requiring any cell-uptake enhancers. Additionally, we observed that the capabilities of these nanogels to provide ADSC imaging is closely related to both their size and surface charge. Our study suggests that the fluorescent nanogels generated by the SAA approach have great potential for ADSC imaging applications due to their excellent cell imaging capabilities and low cytotoxicity.

Self-Assembly Assisted Fabrication of Dextran-Based Nanohydrogels with Reduction-Cleavable Junctions for Applications as Efficient Drug Delivery Systems

In order to overcome the key challenge in improving both fabrication efficiency and their drug delivery capability of anti-cancer drug delivery systems (ACDDS), here polyacrylic acid (PAA) grafted dextran (Dex) nanohydrogels (NGs) with covalent crosslinked structure bearing redox sensitive disulfide crosslinking junctions (Dex-SS-PAA) were synthesized efficiently through a one-step self-assembly assisted methodology (SAA). The Dex-SS-PAA were subsequently conjugated with doxorubicin through an acid-labile hydrazone bond (Dex-SS-PAA-DOX). The in vitro drug release behavior, anti-cancer effects in vivo, and biosafety of the as-prepared acid- and redox-dual responsive biodegradable NGs were systematically investigated. The results revealed that the Dex-SS-PAA-DOX exhibited pH- and redox-controlled drug release, greatly reduced the toxicity of free DOX, while exhibiting a strong ability to inhibit the growth of MDA-MB-231 tumors. Our study demonstrated that the Dex-SS-PAA-DOX NGs are very promising candidates as ACDDS for anti-cancer therapeutics.

Structure and acoustical properties control of magnetite/PLA composite microbubbles

Poly(lactic acid) (PLA) microbubbles and magnetite/PLA composite microbubbles with various structures and controllable average size were prepared by a modified double emulsion–solvent evaporation process, and sound attenuation spectrum was performed to investigate the influence of size, composite structure, and magnetite loading on the acoustical properties of microbubbles. With the increase of time or energy of the emulsification, the inner structure of composite microbubbles changed continuously from honeycomb to solid structure, accompanied by the change of surface morphology and the decrease of average particle size. The sound attenuation and resonance frequency of concentric microbubbles were higher than those of other structures, while microbubbles with multicavities had the lowest sound attenuation and resonance frequency. The difference in the acoustical properties was related to their different structures and water permeability. In vitro ultrasonography of composite microbubbles showed a higher video intensity than that of PLA microbubbles, which was consistent with their sound attenuation spectra.

Scalable and cleavable polysaccharide nanocarriers for the delivery of chemotherapy drugs

While polysaccharide-based nanocarriers have been recognized for their crucial roles in tumor theranostics, the industrial-scale production of nanotherapeutics still remains a significant challenge. Most current approaches adopt a postpolymerization self-assembly strategy that follows a separate synthetic step and thus suffers from subgram scale yields and a limited range of application. In this study, we demonstrate the kilogram-scale formation of polysaccharide-polyacrylate nanocarriers at concentrations of up to 5 wt% through a one-pot approach - starting from various acrylate monomers and polysaccharides - that combines aspects of hydrophobicity-induced self-assembly with the free radical graft copolymerization of acrylate monomers from polysaccharide backbones into a single process that is thus denoted as a graft copolymerization induced self-assembly. We also demonstrate that this novel approach is applicable to a broad range of polysaccharides and acrylates. Notably, by choosing a crosslinker that bears a disulfide group and two vinyl capping groups to structurally lock the nanocarriers, the products are rendered cleavable in the reducing environments encountered at tumor sites and thus provide ideal candidates for the construction of anticancer nanotherapeutic systems. In vitro and in vivo studies demonstrated that the use of this nanocarrier for the delivery of doxorubicin hydrochloride (DOX) significantly decreased the side effects of DOX and improved the bio-safety of the chemotherapy accordingly. STATEMENT OF SIGNIFICANCE While polysaccharide-based nanocarriers have been recognized for their crucial roles in tumor theranostics, the industrial-scale production of these nanotherapeutics still remains a significant challenge. Most current approaches adopt a post-polymerization self-assembly strategy which that follows a separate synthetic step, and thus suffers from sub-gram scale yields and a limited range of application. In this study, the hydrophobic effect was combined with free radical polymerization to facilitate the graft copolymerization-induced self-assembly (GISA) of acrylate monomers with various hydrophobicities to construct cleavable polysaccharide-polyacrylate nanocarriers at a high efficiency with excellent potential for industrial-scale production. We envision that these nanocarriers will contribute to the development of tumor nanotheranostics that combine the biological functionalities of polysaccharides with the unmatched application-specific flexibility of nanocarriers.