Bing Yan

An automated high-throughput method applied to the production and analysis of libraries of natural ­products for high-throughput biological screening is described. The production of the library includes solid-phase extraction of crude extracts to remove polyphenols, followed by automated preparative high-performance liquid chromatography (HPLC) fractionation. Libraries of fractions are analyzed by an ultra-performance liquid chromatography–UV diode-array detection–evaporative light scattering detection–mass spectrometry system (UPLC/PDA/ELSD/MS) to provide information that facilitates characterization of compounds in active fractions. This system fractionates 2,600 unique natural product samples per year, providing fractions in 0.5–10 mg scale for creation of libraries that could be used for the screening of multiple targets to identify hits for various applications including drug discovery.

Background: Increasing concern has been expressed regarding the potential adverse health effects that may be associated with human exposure to inhaled multi-walled carbon nanotubes (MWCNTs). Thus it is imperative that an understanding as to the underlying mechanisms and the identification of the key factors involved in adverse effects are gained. In the alveoli, MWCNTs first interact with the pulmonary surfactant. At this interface, proteins and lipids of the pulmonary surfactant bind to MWCNTs, affecting their surface characteristics. Aim of the present study was to investigate if the pre-coating of MWCNTs with pulmonary surfactant has an influence on potential adverse effects, upon both (i) human monocyte derived macrophages (MDM) monocultures, and (ii) a sophisticated in vitro model of the human epithelial airway barrier. Both in vitro systems were exposed to MWCNTs either pre-coated with a porcine pulmonary surfactant (Curosurf) or not. The effect of MWCNTs surface charge was also investigated in terms of amino (−NH₂) and carboxyl (−COOH) surface modifications. Results: Pre-coating of MWCNTs with Curosurf affects their oxidative potential by increasing the reactive oxygen species levels and decreasing intracellular glutathione depletion in MDM as well as decreases the release of Tumour necrosis factor alpha (TNF-α). In addition, an induction of apoptosis was observed after exposure to Curosurf pre-coated MWCNTs. In triple cell-co cultures the release of Interleukin-8 (IL-8) was increased after exposure to Curosurf pre-coated MWCNTs. Effects of the MWCNTs functionalizations were minor in both MDM and triple cell co-cultures. Conclusions: The present study clearly indicates that the pre-coating of MWCNTs with pulmonary surfactant more than the functionalization of the tubes is a key factor in determining their ability to cause oxidative stress, cytokine/chemokine release and apoptosis. Thus the coating of nano-objects with pulmonary surfactant should be considered for future lung in vitro risk assessment studies.

Biomaterials that can drive stem cells to an appropriate differentiation level and decrease apoptosis of transplanted cells are needed in regenerative medicine. Nanomaterials are promising novel materials for such applications. Here we reported that carboxylated multiwalled carbon nanotube (MWCNT 1) promotes myogenic differentiation of mouse myoblast cells and inhibits cell apoptosis under the differentiation conditions by regulating basic helix-loop-helix transcription factors. MWCNT 1 attenuates bone morphogenetic protein receptor (BMPR) signaling activity by binding to BMPR2 and attenuating the phosphorylation of BMPR1. This molecular understanding allowed us to tune stem cell differentiation to various levels by chemical modifications, demonstrating human control of biological activities of nanoparticles and opening an avenue for potential applications of nanomaterials in regenerative medicine.

Simpler and faster! Multifunctionalized nanoparticles are crucial for nanobiomedical applications, but their syntheses are tedious and time-consuming. A multicomponent reaction on nanostructures is an excellent way to prepare such nanomaterials. The gold nanosystem illustrated in the scheme was built and shown to enhance cancer cell targeting and killing by combining the effects of a therapeutic drug with X-ray radiation.

To conquer complex and devastating diseases such as cancer, more coordinated and combined attack strategies are needed. We suggest that these can be beautifully achieved by using nanoconstruct design. We present an example showing that neuroblastoma cells are selectively killed by a nanoconstruct that specifically targets neuroblastoma cells, pushes cells to the vulnerable phase of the cell cycle, and greatly enhances radiation-induced cell death. The success of this multipronged attack approach launched by cell-embedded nanoconstructs demonstrates the power and flexibility of nanotechnology in treating cancer, a difficult task for a small molecule.

We report a generic approach for identification of target proteins of therapeutic molecules using nanoprobes. Nanoprobes verify the integrity of nanoparticle-bound ligands in live cells and pull down target proteins from the cellular proteome, providing very important information on drug targets and mechanisms of action. As an example, target proteins as α-tubulin and HSP 90 have been identified and validated.

Autophagy is a self-renewal process in cells by recycling redundant materials through lysosomal machinery. The basal level of autophagy in eukaryotic cells plays a “housekeeping” role by degrading redundant cellular materials and providing nutrients and energy. However acute and sustained autophagy may cause autophagic cell death. These two features of autophagy are consistent with its complex roles in both oncogenesis and cancer development. Many small molecule autophagy regulators are developed to turn autophagy on/off for therapeutic purpose. The roles of chemotherapeutic agents in regulating autophagy and facilitating cancer treatment can be classified into three categories: direct autophagy enhancers, indirect autophagy enhancers and autophagy inhibitors. The representative autophagy regulators and their roles in cancer treatment were reviewed.

The past a few years have witnessed the wide use of metallic nanoparticles as ideal reporters for colorimetric detection, which generally involves an analyte-triggered alteration of aggregation degree of applied nanoparticles, and thus the change of colloidal color. However, these aggregation-based colorimetric probe are associated with a number of drawbacks, including poor stability of nanoaggregates, requirement of complicated functionalization and non-linearity of output signals. To address these problems, we herein employ mesoporous silica-coated gold nanorods (MS AuNRs) as novel nanocomposites for non-aggregation-based label-free colorimetric sensing relying on their chemical redox-modulated surface chemistry. In our sensing system, Hg²⁺ ions are reduced to Hg⁰ depositing on the surface of MS AuNPs and result in a great color change of MS AuNRs, while the subsequent introduction of S²⁻ leads to a reverse process owing to the extraction of Hg⁰ by S²⁻. The experimental results for colorimetric sensing of Hg²⁺ and S²⁻ imply considerable sensitivity and specificity, suggesting the high potential of our approach for rapid environmental monitoring and bioanalysis in the future.