Chuanliu Wu

Stable and Functionable Mesoporous Silica-Coated Gold Nanorods as Sensitive Localized Surface Plasmon Resonance (LSPR) Nanosensors

Core-shell structured Au NRs with a surface-exposed gold core and a mesoporous silica shell (MS Au NRs) were demonstrated as a promising platform for localized surface plasmon resonance (LSPR) based molecular sensing. Mesoporous silica shell not only allows the Au NRs core to be directly exposed to their surrounding environment but also stabilizes Au NRs dispersion in various water-organic mixtures and pure organic solvents. The LSPR band of MS Au NRS displays a stable and linear response in spectral shift to the changes in their surrounding refractive index with a sensitivity of 325 nm/RIU. To demonstrate the application of MS Au NRs as LSPR nanosensors in molecular sensing, the plasmon response to molecular adsorbates (GSH) was demonstrated. MS Au NRs provide a more stable and sensitive response than CTAB-capped Au NRs in GSH sensing. In addition, we have also demonstrated that the LSPR response of Au NRs is highly sensitive to changes of local refractive index in mesoporous silica shell, which renders the feasibility of using MS Au NRs as effective molecule-sensing platforms when mesoporous silica shells were functionalized with various chemical and biological ligands.

Multifunctional Core−Shell Nanoparticles as Highly Efficient Imaging and Photosensitizing Agents

Here we report the preparation of a novel multifunctional core-shell nanocomposite material that contains a nonporous dye-doped silica core and a mesoporous silica shell containing photosensitizer molecules, hematoporphyrin (HP). This architecture allows simultaneous fluorescence imaging and photosensitization treatment. The photosensitizer molecules are covalently linked to the mesoporous silica shell and exhibit excellent photo-oxidation efficiency. The efficiency of photo-oxidation of the core-shell hybrid nanoparticles was demonstrated to be significantly improved over that in the homogeneous solution. The mesoporous silica nanovehicle acts not only as a carrier for the photosensitizers but also as a nanoreactor to facilitate the photo-oxidation reaction. The doping of fluorescence dyes into the nonporous core endows the imaging capability, which has been demonstrated with cell imaging experiments. This approach could be easily extended to conjugate other functional regents if necessary. These multifunctional nanovehicles possess unique advantages in acting as nanocarriers in photodynamic therapy to allow simultaneous high-resolution targeting and treatment.

Fluorescent core-shell silica nanoparticles as tunable precursors: towards encoding and multifunctional nano-probes

Core-shell silica nanoparticles comprised of a RuBpy doped silica core and a Pas-DTPA doped silica shell were synthesized and post-functionalized with an encoding fluorescence combination and multiplex imaging function.

Interplay of chemical microenvironment and redox environment on thiol-disulfide exchange kinetics.

The interplay between the chemical microenvironment surrounding disulfides and the redox environment of the media on thiol-disulfide exchange kinetics was examined by using a peptide platform. Exchange kinetics of up to 34 cysteine-containing peptides were measured in several redox buffers. The electrostatic attraction/repulsion between charged peptides and reducing agents such as glutathione was found to have a very pronounced effect on thiol-disulfide exchange kinetics (differences of ca. three orders of magnitude). Exchange kinetics could be directly correlated to peptide charge over the entire range examined. This study highlights the possibility of finely and predictably tuning thiol-disulfide exchange, and demonstrates the importance of considering both the local environment surrounding the disulfide and the nature of the major reducing species present in the environment for which their use is intended (e.g., in drug delivery systems, sensors, etc).

Twin disulfides for orthogonal disulfide pairing and the directed folding of multicyclic peptides

Multicyclic peptides are emerging as an exciting platform for drug and targeted ligand discovery owing to their expected greater target affinity/selectivity/stability versus linear or monocyclic peptides. However, although the precise pairing of cysteine residues in proteins is routinely achieved in nature, the rational pairing of cysteine residues within polypeptides is a long-standing challenge for the preparation of multicyclic species containing several disulfide bridges. Here, we present an efficient and straightforward approach for directing the intermolecular and intramolecular pairing of cysteine residues within peptides using a minimal CXC motif. Orthogonal disulfide pairing can be exploited in complex redox media to rationally produce dimeric peptides and bi/tricyclic peptides from fully reduced peptides containing 1-6 cysteine residues. This strategy, which does not rely on extensive manipulation of the primary sequence, post-translational modification or protecting groups, should greatly benefit the development of multicyclic peptide therapeutics and targeting ligands.

LSPR Sensing of Molecular Biothiols Based on Noncoupled Gold Nanorods

Au NRs protected with mPEG-SH molecules (mPEG-Au NRs) were demonstrated to be a promising platform for LSPR-based sensing of molecular biothiols in aqueous solution. Surface mPEG-SH molecules endow Au NRs with great stability and biocompatibility and no nonspecific adsorption of biomacromolecules. The LSPR band of mPEG-Au NRs displays a stability and linear response in the spectral shift with respect to a change in their surrounding refractive index with a sensitivity of 252 nm/RIU. The loose structure of mPEG-SH around the Au NRs offers free sites, thereby allowing molecular biothiols to bind onto the surfaces of Au NRs. The LSPR response and the sensitivity of Au NRs to biothiols such as GSH, Cys, Hcy, TGA, GSSG, and BSA were then studied.

Broad control of disulfide stability through microenvironmental effects and analysis in complex redox environments.

Disulfide bonds stabilize the tertiary- and quaternary structure of proteins. In addition, they can be used to engineer redox-sensitive (bio)materials and drug-delivery systems. Many of these applications require control of the stability of the disulfide bond. It has recently been shown that the charged microenvironment of the disulfide can be used to alter their stability by ∼3 orders of magnitude in a predictable and finely tunable manner at acidic pH. The aim of this work is to extend these findings to physiological pH and to demonstrate the validity of this approach in complex redox milieu. Disulfide microenvironments were manipulated synergistically with steric hindrance herein to control disulfide bond stability over ∼3 orders of magnitude at neutral pH. Control of disulfide stability through microenvironmental effects could also be observed in complex redox buffers (including serum) and in the presence of cells. Such fine and predictable control of disulfide properties is not achievable using other existing approaches. These findings provide easily implementable and general tools for controlling the responsiveness of biomaterials and drug delivery systems toward various local endogenous redox environments.

Enhanced One- and Two-Photon Excitation Emission of a Porphyrin Photosensitizer by FRET from a Conjugated Polyelectrolyte

Porphyrin-based systems are widely used as photosensitizers for photodynamic therapy, photocatalysis, and drug release. Strategies to enhance one- or two-photon excitation emission of porphyrin sensitizers have been of great interest and significance. Here we report an electrostatic assembly, which comprises a cationic conjugated polyelectrolyte, PFP, and a negatively charged hematoporphyrin (HP). An enhancement of over 9-fold in the HP emission intensity for one-photon excitation Forster resonance energy transfer (FRET), and an enhancement factor of 30-fold for two-photon excitation FRET were obtained. This electrostatic assembly can be easily modified in the future to construct DNA- or protein-programmed enhancement of porphyrin emission, which will be of great interest in porphyrin-based applications.

pH-Switchable Fluorescent Probe for Spatially-Confined Visualization of Intracellular Hydrogen Peroxide

Intracellular H2O2 plays an important role in regulating a variety of cellular functions. Fluorescent probes that can make response to intracellular levels of H2O2 would provide valuable tools for revealing the functions of H2O2 in living organisms. However, traditional pH-insensitive probes and lysosome-targetable probes can only provide spatially nonspecific visualization of intracellular H2O2 and specific sensing of lysosomal H2O2, respectively. In this work, we developed a H2O2-responsive and pH-switchable fluorescent probe (HP-L1) which can make response sequentially to intracellular H2O2 and lysosomal pH. The fluorescent probe is comprised of a H2O2-responsive boronate moiety and a pH-switchable spirobenzopyran fluorophore. When the probe was applied for intracellular H2O2 sensing, only fluorescent emission from lysosomes is visible, and the fluorescence from other regions is not able to be obviously detected, which is due to the pH-switchable property of the spirobenzopyran fluorophore. Thus, the developed fluorescence probe enables the spatially confined (i.e., lysosome-specific) visualization of the intracellular H2O2. We envisioned that this kind of fluorescent probe (or the proposed sensing strategy) would allow the visualization of the overall levels of intracellular H2O2 without interferences of possible fluorescent signals from other sources (e.g., dyes for cellular staining and multiplex analysis).

Light-triggered covalent assembly of gold nanoparticles in aqueous solution

UV light irradiation triggers Au NPs that are respectively functionalized on the surface by o-nitrobenzyl alcohol and benzylamine to proceed with a covalent ligation reaction, which leads to assembling of Au NPs into anisotropic one-dimensional (1D) arrays in aqueous solution via indazolone linkages.