nxian Li

UV‐Triggered Dopamine Polymerization: Control of Polymerization, Surface Coating, and Photopatterning

UV irradiation is demonstrated to initiate dopamine polymerization and deposition on different surfaces under both acidic and basic pH. The observed acceleration of the dopamine polymerization is explained by the UV-induced formation of reactive oxygen species that trigger dopamine polymerization. The UV-induced dopamine polymerization leads to a better control over polydopamine deposition and formation of functional polydopamine micropatterns.

Reactive superhydrophobic surface and its photoinduced disulfide-ene and thiol-ene (bio)functionalization

Reactive superhydrophobic surfaces are highly promising for biotechnological, analytical, sensor, or diagnostic applications but are difficult to realize due to their chemical inertness. In this communication, we report on a photoactive, inscribable, nonwettable, and transparent surface (PAINTS), prepared by polycondensation of trichlorovinylsilane to form thin transparent reactive porous nanofilament on a solid substrate. The PAINTS shows superhydrophobicity and can be conveniently functionalized with the photoclick thiol-ene reaction. In addition, we show for the first time that the PAINTS bearing vinyl groups can be easily modified with disulfides under UV irradiation. The effect of superhydrophobicity of PAINTS on the formation of high-resolution surface patterns has been investigated. The developed reactive superhydrophobic coating can find applications for surface biofunctionalization using abundant thiol or disulfide bearing biomolecules, such as peptides, proteins, or antibodies.

Boronate-dextran: an acid-responsive biodegradable polymer for drug delivery.

Stimuli-responsive drug carriers have great potential to deliver bioactive materials on demand and to a specific location within the human body. Acid-responsive drug carriers can specifically release their payload in the acidic microenvironments of tumors or in the endosomal or lysosomal compartments within a cell. Here we describe an approach to functionalize vicinal diols of dextran with hydrophobic boronate esters in order to produce a water insoluble boronate dextran polymer (B-Dex), which spontaneously forms acid-responsive nanoparticles in water. We show the encapsulation of a hydrophobic anticancer drug doxorubicin into the particles. Hydrolysis of the boronate esters under mild acidic conditions recovers the hydrophilic hydroxyl groups of the dextran and disrupts the particles into water soluble fragments thereby leading to a pH-responsive release of the drug. According to dynamic light scattering (DLS) and UV/Vis spectroscopy, mild acidic conditions (pH 5.0) lead to a three-fold increase in the degradation of the particles and a four-fold increase in the release of the drug compared to the behavior of particles at pH 7.4. In vitro tests in Hela cells show no toxicity of the empty B-Dex nanoparticles, while the toxicity of doxorubicin-loaded B-Dex nanoparticles is comparable to that of the doxorubicin · HCl drug. Confocal fluorescence microscopy reveals that 100% of the Hela cells uptake doxorubicin-loaded B-Dex nanoparticles with a preferential accumulation of the nanoparticles in the cytoplasm.

A biomimetic lipid library for gene delivery through thiol-yne click chemistry

The delivery of nucleic acids such as plasmid DNA and siRNA into cells is a cornerstone of biological research and is of fundamental importance for medical therapeutics. Although most gene delivery therapeutics in clinical trials are based on viral vectors, safety issues remain a major concern. Non-viral vectors, such as cationic lipids and polymers, offer safer alternatives but their gene delivery efficiencies are usually not high enough for clinical applications. Thus, there is a high demand for more efficient and safe non-viral vectors. Here, we present a facile two-step method based on thiol-yne click chemistry for parallel synthesis of libraries of new biomimetic cationic thioether lipids. A library of novel lipids was synthesized using the developed method and more than 10% of the lipids showed highly efficient transfection in different cell types, surpassing the efficiency of several popular commercial transfection reagents. One of the new lipids showed highly efficient siRNA delivery to multiple cell types and could successfully deliver DNA plasmid to difficult-to-transfect mouse embryonic stem cells (mESC). Analysis of structure-activity relationship revealed that the length of the hydrophobic alkyl groups was a key parameter for efficient cell transfection and was more important for transfection efficiency than the nature of cationic head groups. The correlation of the size and surface charge of liposomes with transfection efficiency is described.

Single-Step Fabrication of High-Density Microdroplet Arrays of Low-Surface-Tension Liquids.

A facile approach for surface patterning that enables single-step fabrication of high-density arrays of low-surface-tension organic-liquid microdroplets is described. This approach enables miniaturized and parallel high-throughput screenings in organic solvents, formation of homogeneous arrays of hydrophobic nanoparticles, polymer micropads of specific shapes, and polymer microlens arrays.

Reversible and Rewritable Surface Functionalization and Patterning via Photodynamic Disulfide Exchange

A reversible surface functionalization and patterning strategy based on a photodynamic disulfide exchange reaction is demonstrated. The method allows for rapid and reversible functionalization, patterning, and exchange or removal of functional groups on the surface.

UV‐Induced Tetrazole‐Thiol Reaction for Polymer Conjugation and Surface Functionalization

A UV-induced 1,3-dipolar nucleophilic addition of tetrazoles to thiols is described. Under UV irradiation the reaction proceeds rapidly at room temperature, with high yields, without a catalyst, and in both polar protic and aprotic solvents, including water. This UV-induced tetrazole-thiol reaction was successfully applied for the synthesis of small molecules, protein modification, and rapid and facile polymer-polymer conjugation. The reaction has also been demonstrated for the formation of micropatterns by site-selective surface functionalization. Superhydrophobic-hydrophilic micropatterns were successfully created by sequential modifications of a tetrazole-modified porous polymer surface with hydrophobic and hydrophilic thiols. A biotin-functionalized surface could be fabricated in aqueous solutions under long-wavelength UV irradiation.

Combinatorial Synthesis and High-Throughput Screening of Alkyl Amines for Nonviral Gene Delivery

Efficient delivery of plasmid DNA and siRNA into cells is essential for biological and biomedical research. Although significant efforts have been made to develop efficient nonviral vectors, such as cationic lipids and polymers, most of the vectors require multistep synthesis, which complicates both fast structural optimizations and combinatorial synthesis of such vectors. Here, we present a facile, single-step method based on an alkylation of amines, allowing for the fast parallel synthesis of libraries of cationic lipid-like molecules (lipidoids). We exploited the method to synthesize 200 lipidoids, which were screened for their transfection efficiency in HEK293T cells. The screen resulted in about 2% of new lipidoids capable of efficient cell transfection similar or higher than the efficiency of Lipofectamine 2000. In addition, we observed an enhancement of cellular transfection by combining single- with double-chain lipidoids, which was attributed to the different roles of the single- and double-tailed lipids in the mixed liposomes.

Bio-inspired strategy for controlled dopamine polymerization in basic solutions

Polydopamine (PD) coatings, inspired by the adhesive behavior of the mussel foot, have attracted a lot of attention because of the simplicity, generalizability, and the capability for their secondary modification. However, many possible applications of PD coatings cannot be realized due to the difficulty in controlling dopamine polymerization under basic conditions. Here, we report a new method for the light-triggered control of both the onset and termination of dopamine polymerization under basic conditions. We demonstrate that dopamine polymerization in basic solutions can be efficiently inhibited by adding small quantities of sodium ascorbate (vitamin C) that reduces reactive dopamine quinone and delays dopamine polymerization. UV irradiation of this solution, however, leads to instantaneous dopamine polymerization, thereby making light-driven spatial and temporal control of dopamine polymerization under basic conditions possible. This method is inspired by the antioxidant role of vitamin C in the human body. The mechanism of the light-driven SA-controlled dopamine polymerization has been studied using spectroscopic and electroanalytical methods. By this new method we can control dopamine polymerization without changing the commonly used conditions for the formation of PD coatings, making this method compatible with all existing applications for PD coatings.

Screenfect A: an efficient and low toxic liposome for gene delivery to Mesenchymal stem cells

Mesenchymal stem cells (MSCs) hold great promise in variety of therapeutic applications including tissue engineering and cancer therapy. Genetic modification of MSCs can be used to enhance the therapeutic effect of MSCs by facilitating a specific function or by transforming MSCs into more effective gene therapy tools. However, the successful generation of genetically modified MSCs is often limited by the poor transfection efficiency or high toxicity of available transfection reagents. In our previous study, we used thiol-yne click chemistry to develop new liposomal vectors, including ScreenFect(®) A (SF) (Li et al., 2012). In this study, we investigated the transfection performance of SF on MSCs. A comparative evaluation of transfection efficiency, cell viability and cellular DNA uptake was performed using the Lipofectamine™ 2000 (L2K) as a control, and the results show that SF is superior to L2K for MSC transfection. The presence of serum did not significantly influence the transfection efficiency of either SF or L2K but greatly reduced the viability of MSC transfected by L2K. The higher efficiency of SF-mediated transfection compared to L2K was also correlated with better proliferation of cells. These results were supported by monitoring the intracellular fate of DNA, which confirmed stable transportation of DNA from lysosomes and efficient nuclear localization. TGF-β1 gene delivery by SF promoted MSC osteogenic differentiation in an osteogenic induction condition. As the first study of SF lipofection on stem cells, this study highlights a promising role of SF in gene delivery to MSCs as well as other stem cells to facilitate tissue engineering and other therapeutic effects based on genetically modified stem cells.