Jingjiao Guan

Growth and alignment of polyaniline nanofibres with superhydrophobic, superhydrophilic and other properties

Polyaniline nanofibres can be prepared by a number of methods based on chemical oxidative polymerization and in situ adsorption polymerization. However, the lack of alignment in these nanostructures makes them unsuitable for many applications. Here, we report a simple approach to chemical oxidative polymerization that can control the growth and simultaneous alignment of polyaniline nanofibres grown on a range of conducting and non-conducting substrates in a wide variety of sizes. The diameters of the tips of the nanofibres can be controlled within the range 10-40 nm, and the average length can be controlled within the range 70-360 nm. Moreover, the coatings display a range of properties including superhydrophilicity and superhydrophobicity. Such nanostructured coatings may be useful for applications such as anti-fog coatings, self-cleaning surfaces, DNA manipulation, transparent electrodes for low-voltage electronics, and chemical and biological sensors.

An oral delivery device based on self-folding hydrogels.

A self-folding miniature device has been developed to provide enhanced mucoadhesion, drug protection, and targeted unidirectional delivery. The main part of the device is a finger like bilayered structure composed of two bonded layers. One is a pH-sensitive hydrogel based on crosslinked poly(methyacrylic acid) (PMAA) that swells significantly when in contact with body fluids, while the other is a non-swelling layer based on poly(hydroxyethyl methacrylate) (PHEMA). A mucoadhesive drug layer is attached on the bilayer. Thus, the self-folding device first attaches to the mucus and then curls into the mucus due to the different swelling of the bilayered structure, leading to enhanced mucoadhesion. The non-swelling PHEMA layer can also serve as a diffusion barrier, minimizing any drug leakage in the intestine. The resulting unidirectional release provides improved drug transport through the mucosal epithelium. The functionality of this device is successfully demonstrated in vitro using a porcine small intestine.

Cationic lipid-coated magnetic nanoparticles associated with transferrin for gene delivery

Cationic lipid-coated magnetic nanoparticles (MPs) associated with transferrin were evaluated as gene transfer vectors in the presence of a static magnetic field. MPs were prepared by chemical precipitation and were surface-coated with cationic lipids, composed of DDAB/soy PC (60:40 mole/mole). These cationic MPs were then combined with polyethylenimine (PEI) condensed plasmid DNA, followed by transferrin. The resulting magnetic electrostatic complexes retained relatively compact particle size and showed complete DNA condensation. Their transfection activity in the presence of a static magnetic field was evaluated by luciferase and green fluorescent protein (GFP) reporter genes. The magnetic complexes exhibited up to 300-fold higher transfection activity compared to commonly used cationic liposomes or cationic polymer complexes, based on luciferase assay. The enhancement in transfection activity was maximized when the cells were exposed to the vectors for a relatively short period of time (15 min), or were treated in media containing 10% serum. Incorporation of transferrin further improved transfection efficiency of the cationic MPs. However, when cells were incubated for 4h in serum-free media, magnetic and non-magnetic vectors showed similar transfection efficiencies. In conclusion, transferrin-associated cationic MPs are excellent gene transfer vectors that can mediate very rapid and efficient gene transfer in vitro in the presence of a magnetic field.

Delivery of antisense oligodeoxyribonucleotide lipopolyplex nanoparticles assembled by microfluidic hydrodynamic focusing

A multi-inlet microfluidic hydrodynamic focusing (MF) system to prepare lipopolyplex (LP) containing Bcl-2 antisense deoxyoligonucleotide (ODN) was developed and evaluated. The lipopolyplex nanoparticles consist of ODN:protamine:lipids (1:0.3:12.5wt/wt ratio) and the lipids included DC-Chol:egg PC:PEG-DSPE (40:58:2mol/mol%). Using K562 human erythroleukemia cells, which contain an abundance of Bcl-2 and overexpression of transferrin receptors (TfR), and G3139 (oblimerson sodium or Genasense(TM)) as a model cell line and drug, respectively, the Bcl-2 down-regulation at the mRNA and protein levels as well as cellular uptake and apoptosis was compared between the conventional bulk mixing (BM) method and the MF method. The lipopolyplex size and surface charge were characterized by dynamic light scattering (DLS) and zeta potential (zeta) measurement, respectively, while the ODN encapsulation efficiency was determined by gel electrophoresis. Cryogenic transmission electron microscopy (Cryo-TEM) was used to determine the morphology of LPs. Our results demonstrated that MF produced LP nanoparticles had similar structures but smaller size and size distribution compared to BM LP nanoparticles. MF LP nanoparticles had higher level of Bcl-2 antisense uptake and showed more efficient down-regulation of Bcl-2 protein level than BM LP nanoparticles.

Delivery of Polyethylenimine/DNA Complexes Assembled in a Microfluidics Device

Polyethylenimine (PEI) and plasmid DNA (pDNA) complexes (PEI/pDNA) are nonviral vectors for gene delivery. The conventional method for producing these complexes involves bulk mixing (BM) of PEI and DNA followed by vortexing which at low N/P ratios results in large particle size distribution, low cytotoxicity, and poor gene transfection, while at high N/P ratios it results in small particle size and better gene transfection but high cytotoxicity. To improve size control, gene transfection efficiency, and cytotoxicity, in this study, we used a microfluidic hydrodynamic focusing (MF) device to prepare PEI/pDNA complexes at N/P = 3.3 and 6.7. We used bulk mixing as control, mouse NIH 3T3 fibroblast cells and mouse embryonic stem (mES) cells as model cell lines, plasmid encoding green fluorescent protein (pGFP) and secreted alkaline phosphatase (pSEAP) as the reporter gene, and commercially available Lipofectamine 2,000 as a positive control. The complexes were characterized by atomic force microscopy (AFM), dynamic light scattering (DLS), and zeta potential (zeta) measurement. Confocal laser scanning microscopy (CLSM) and fluorescent labeling techniques were used to visualize the complex size distribution, complexation uniformity, and cellular distribution. The results showed that MF produced complexes were smaller and more uniformly complexed and had higher cell viability and improved exogenous gene expression.

Large Laterally Ordered Nanochannel Arrays from DNA Combing and Imprinting

One-dimensional nanostructures such as nanochannels (and nanotubes) are characterized by extremely small transverse size and resultant high degree of spatial confinement that endow them a unique set of properties. When patterned laterally, these nanostructures are widely used as critical transport devices for a variety of applications such as sensing, nanomanipulation, and information processing.[1–8] While numerous fabrication techniques have been developed, few can generate large and highly ordered arrays of both nanochannels and nanowires with no defects and low-cost. The most notable high-resolution lithographic techniques include electron beam lithography (EBL) and focused ion beam milling (FIB),[9–13] but they are associated with either low throughput or high-cost. Another lithographic technique, nanoimprint lithography (NIL), is of high throughput and relatively low-cost, but it requires the use of highly specialized equipment and molds prepared typically by EBL.[14– 17] Many inexpensive techniques have been developed, but they are inadequate in terms of high precision, low defect rate, or large area fabrication of both nanochannels/tubes and nanowires/strands.[7,18–25] Moreover, these nanostructures need to be connected to the micro/macroscale structures, such as reservoirs and channels, to form functional devices. This is not a trivial task and the lack of a low-cost solution to this problem significantly limits the applicability of many nanoconstructs.

Fabrication of Multilayered Microparticles by Integrating Layer‐by‐Layer Assembly and MicroContact Printing

Recent years have seen emergence of various top-down methods for producing micro/nanoparticles for biomedical applications. [ 1 ] Notably, Desai et al. used photolithography to generate silicon and polymer particles with asymmetrical structures for drug delivery. [ 2 , 3 ] Similarly, Ferrari et al. created porous silicon particles carrying anticancer drug and imaging agent. [ 4 , 5 ] Though powerful in producing particles with welldefi ned structures and sizes, these two methods suffer from the need for cleanroom facilities, which are expensive and not accessible by many researchers. Photolithography was also combined with microfl uidics to produce particles. [ 6 ] This method is likely limited to a low production yield because the particles were created in a one-by-one fashion. Hansford et al. developed a series of soft lithographic methods including microcontact printing ( μ CP) to fabricate polymer and hydrogel microparticles. [ 7 , 8 ] Although the cleanroom facilities are not critically required, these methods are not suitable for fabricating particles using polyelectrolytes, which constitute an important group of biomedical materials. Polymer and hydrogel particles were also produced by curing liquid precursor fi lled in surface cavities of a mold. [ 9–11 ] These methods generally suffer from exposure of cargo materials to harsh conditions such as UV light. The requirement for maintaining structural integrity of the particles also limits the amount of the cargo materials that can be incorporated. Moreover, the methods lack versatile and precise control of the internal structure of the particles. On the other hand, layer-by-layer (LbL) assembly allows for integrating various biomolecules and polyelectrolytes in a well-defi ned manner. [ 12 ] It was combined with photolithography to produce microparticles. [ 13 , 14 ]

Simultaneous fabrication of hybrid arrays of nanowires and micro/nanoparticles by dewetting on micropillars

Large and well-defined arrays of both nanowires and micro/nanoparticles or only micro/nanoparticles are fabricated from aqueous solutions through a one-step dewetting process on an array of polydimethylsiloxane (PDMS) micropillars.

Microcontact printing of polyelectrolytes on PEG using an unmodified PDMS stamp for micropatterning nanoparticles, DNA, proteins and cells

A facile microcontact printing method has been developed based on directly printing polyelectrolytes on a glass or polystyrene surface coated with poly(ethylene glycol) (PEG) silane using an unmodified poly(dimethyl siloxane) (PDMS) stamp. The method is applicable to a variety of polyelectrolytes including poly(allylamine hydrochloride) (PAH), poly(diallyldimethylammonium chloride) (PDAC), branched and linear poly(ethylene imine) (PEI), poly-L-lysine (PLL), chitosan, double stranded DNA, and poly(sodium 4-styrene sulfonate) (PSS). The printed polyelectrolyte structures, which include monolayer, bilayer, and stretched molecular bundles, are stable in aqueous solutions and have been used as templates for micropatterning quantum dot nanoparticles, DNA, proteins, and live cells.

Patterning nanowire and micro-∕nanoparticle array on micropillar-structured surface: Experiment and modeling

DNA molecules in a solution can be immobilized and stretched into a highly ordered array on a solid surface containing micropillars by molecular combing technique. However, the mechanism of this process is not well understood. In this study, we demonstrated the generation of DNA nanostrand array with linear, zigzag, and fork-zigzag patterns and the microfluidic processes are modeled based on a deforming body-fitted grid approach. The simulation results provide insights for explaining the stretching, immobilizing, and patterning of DNA molecules observed in the experiments.