High-Resolution Vertical Polarization Excited Dark-Field Microscopic Imaging of Anisotropic Gold Nanorods for the Sensitive Detection and Spatial Imaging of Intracellular microRNA-21.

As an important biomarker for early diagnosis of cancers, sensitive detection and high-resolution imaging of microRNA-21 in cancer cells have become important and challengeable. In this work, highly sensitive detection and spatial imaging of intracellular microRNA-21 were realized by the reduced signal background through vertical polarization excitation with a polarizer. The lateral local surface plasmon resonance property of gold nanorods (AuNRs) displayed a pronounced green color with low scattering intensity, which was adjusted to red color with strong scattering intensity when the core-satellite gold nanoparticle (AuNP) assembly was constructed on the side of AuNRs through a catalyzed hairpin assembly (CHA) circuit in the presence of microRNA-21. This unique approach allows for effectively reducing the strong background signal to improve the sensitivity of detection. Additionally, the proposed strategy can not only realize the sensitive detection of microRNA-21 with the limit of detection as low as 2 pM (3σ) but also achieve the high spatial imaging of cancer cells, which provided a specific strategy for the construction and imaging of intracellular imaging probes. It is believed that the simple and sensitive approach on the basis of lateral local surface plasmon resonance property of anisotropic AuNRs with excellent sensitivity combined with high spatial imaging holds promising potentials to visualize intracellular microRNAs with low abundance.

"Hepatitis virus indicator"----the simultaneous detection of hepatitis B and hepatitis C viruses based on the automatic particle enumeration.

As the common hepatitis viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV) are important causes of liver diseases, which greatly threaten human health and public hygiene. Furthermore, due to the similar transmission routes of HBV and HCV, it is highly susceptible to suffer from the cross-infection of HBV and HCV when humans are infected by hepatitis viruses. So it is urgent to develop strategies with high sensitivity to distinguish HBV/HCV and detect their overlapping infection. Herein, a new biosensor named "hepatitis virus indicator" for simultaneous detection of HBV and HCV based on the automatic particle enumeration was developed by the combination of Exo III assisted signal amplification strategy and particle counting technology with a dark-field microscopy. The limit of detections (LOD) were as low as 0.194 pM for HBV and 0.169 pM for HCV, respectively. In addition, the proposed method was capable of simultaneously detecting HBV and HCV based on the colorful light scattering from plasmonic nanoparticles. The proposed assay was simple, sensitive and selective for the simultaneous detection of HBV and HCV, which provided a new idea for the early diagnosis of diseases, such as hepatitis A virus (HAV), hepatitis D virus (HDV) and hepatitis E virus (HEV).

Multifunctional small molecule for controlled assembly of oligomeric nanoparticles and crosslinked polymers.

One multifunctional small molecule can undergo a natural condensation reaction under the control of reducing agent to generate amphiphilic oligomers which quickly self-assemble supramolecular nanoparticles or form crosslinked, reversibly degradable polymers.

Size-Dependent Plasmonic Resonance Scattering Characteristics of Gold Nanorods for Highly Sensitive Detection of microRNA-27a.

MicroRNAs, as one kind of significant biomarkers, play indispensable roles in the diagnosis and treatment of cancers. Yet, owing to low expression and high sequence homology, high sensitivity and specificity for microRNA detection are greatly challenging. Herein, a sensitive sensing platform with high specificity was developed for microRNA-27a (miRNA-27a) based on the miRNA-27a-triggered chemical etching of gold nanorods to a smaller size, which was accompanied by a significant blue shift and a large decrease of intensity in the localized surface plasmon resonance (LSPR) scattering and remarkable color variability from red to green. When combined with strand displacement reactions as well as liposome signal amplification and transduction, the proposed bioassay presented high selectivity toward miRNA-27a in a dynamic range from 100 fM to 3 pM and a low limit of detection of 16.5 fM (3σ/k) by dark-field microscopy. Additionally, the remarkable discrimination of single nucleotide difference suggested superior selectivity and was able to detect miRNA-27a extracted from breast cancer cells. The strategy put forward is universal, presenting amusing application prospects in the early diagnosis of various cancers by adapting the corresponding nucleotide sequences.

Metabolites and the pharmacokinetics of kobophenol A from Caragana sinica in rats.

This research aims to study the metabolism and pharmacokinetics of phytoestrogen kobophenol A (1), the main active compound of Caragana sinica (Buc'hoz) Rehd. (Fabaceae), in rats. Metabolites of 1 in rats' feces were isolated and purified by multi-chromatograph techniques; three new metabolites of 1, named koboquinone A (M1), koboquinone B (M2) and koboquinone C (M3), were isolated, purified from rats' feces after they being orally administered with 1. Structure identification of the metabolites was fulfilled by spectroscopic analysis. M1 and M2 are structurally different to those natural occurring stilbene tetramers, which also have para-quinone structure. M1 also showed the activity of stimulating the proliferation of cultured osteoblasts. The pharmacokinetics of 1 in rats could be described by a two-compartmental model (P<0.05). The half-life was 0.68 h for i.v. administration and 5.78 h for oral administration. The oral bioavailability of 1 was calculated to be 2.0%; rats tissue distribution experiments show that 1 was prominently concentrated in livers. Both of the low oral bioavailability and the rapid reduction of 1 in blood indicated a suitable formulation is needed while it is developed as a new drug.

Controlled intracellular self-assembly of gadolinium nanoparticles as smart molecular MR contrast agents.

Herein we developed a new "smart" Gd-based MR contrast agent (i.e., 1) which is susceptive to furin, a protease overexpressed in tumor. Under the action of furin, 1 condenses to form dimers (1-Ds) and the latter self-assemble into gadolinium nanparticles (Gd-NPs). Relaxivity of 1-D is more than 2 folds of those of 1 and magnevist at 1.5 T, and 1.4 folds of that of 1 at 3 T. Intracellular condensation of 1 in furin-overexpressed MDA-MB-468 cells was proven with direct two-photon laser microscopy (TPLM) fluorescence imaging of the cells incubated with the europium analog of 1 (i.e., 2). Intracellular Gd-NPs of 1 were uncovered and characterized for the first time. MRI of MDA-MB-468 tumors showed that 1 has enhanced MR contrast within the tumors than that of its scrambled control 1-Scr.

DEVD-based hydrogelator minimizes cellular apoptosis induction.

Herein, we report the rational design of a DEVD-based heptapeptide hydrogelator 1 which is susceptible to caspase-3 (CASP3), and its isomeric control hydrogelator 2 with a DEDV-based heptapeptide sequence. Self-assembly of 1 in water results in flexuous, long nanofibers to form supramolecular hydrogel I with higher mechanical strength than that of hydrogel II which is composed of rigid, short nanofibers of 2. In vitro enzymatic analysis indicated that 1 is susceptive to CASP3 while 2 is not. 3-(4,5-dimethylthiazol-2-yl) 2,5 diphenyl tetrazolium bromide (MTT) and Western blot analyses indicated that DEDV-based hydrogelator 2 induces cell death via apoptotic pathway while the DEVD-based hydrogelator 1 minimizes cellular apoptosis induction.

Caspase-3 controlled assembly of nanoparticles for fluorescence turn on.

A caspase-3 controlled condensation was applied to self-assemble biotinylated nanoparticles for capturing FITC-labelled streptavidin and subsequently turning on the fluorescence signal.

Semisynthesis and antitumor activities of new styryl-lactone derivatives.

Nineteen new derivatives of the naturally occurring compound, goniothalamin, were prepared by chemical modification and semi-synthetic methods. The antitumor activities of these derivatives and goniothalamin were evaluated in vitro against human tumor cell lines, and most of them showed an inhibitory effect against HL-60 cancer cells. The derivatives 10-nitro-goniothalamin and 10-amino-goniothalamin gave selective inhibition concentration (IC50) of 1.10 and 1.14 microg/ml, respectively, against human stomach cancer SGC-7901 cells, while that of etoposide (vp-16) as the positive control was 6.07 microg/ml. Finally, the partition coefficients, logP (pi values), of these derivative molecules, were evaluated by calculating the additive approximate organic fragment logP value.