Synthesis of porphyrin-conjugated silica-coated Au nanorods for synergistic photothermal therapy and photodynamic therapy of tumor.

Synergistic therapy of tumor has attracted the attention of an increasing number of researchers because of its higher efficiency compared to single therapy. Herein, 4-carboxyphenyl porphyrin-conjugated silica-coated gold nanorods (AuNR@SiO2-TCPP) were synthesized. The synergistic treatment of photothermal therapy and photodynamic therapy on A549 cancer was researched in vivo and in vitro. In the AuNR@SiO2-TCPP, Au NRs and TCPP act as photothermal agent and photosensitizer, respectively. The temperature of the AuNR@SiO2-TCPP (0.11 nmol L-1) rises to 56.8 °C for 10 min under the illumination of 808 nm laser (2 Wcm-2). In MTT assays, the viability of A549 cancer cell treated with AuNR@SiO2-TCPP (100 µg ml-1) is only 21%. In animal experiments, the relative tumor volumes in mice receiving AuNR@SiO2-TCPP (5 mg kg-1) with 660 and 808 nm irradiations were significantly inhibited and the average value is decreased to 0.78 while the average value of the control group is increased to 7.2. These results demonstrate that the AuNR@SiO2-TCPP is a potential nanomedicine against tumor for clinical application in the near future.

Systematic investigation of intracellular trafficking behavior of one-dimensional alumina nanotubes.

Nanotube materials exhibit high drug loading capacity and controlled drug release properties, providing new opportunities for drug delivery. However, the intracellular trafficking paths of 1-dimensional (1D) nanostructured materials are poorly understood compared to their spherical counterparts, impeding the broad application of 1D materials as drug carriers. Here, we report the intracellular trafficking mechanism of nontoxic and biocompatible nanomaterials called anodic alumina nanotubes (AANTs), a model for 1D materials with a geometry that can be precisely engineered. The results indicated that AANTs enter the cells mainly by caveolin endocytosis and micropinocytosis and that cells use a novel macropinocytosis-late endosomes (LEs)-lysosomes route to transport AANTs. Moreover, liposomes (marked by DsRed-Rab18) are fully involved in the classical pathway of early endosomes (EEs)/LEs developing into lysosomes. The AANTs were delivered to the cells via two pathways: slow endocytosis recycling and GLUT4 exocytosis vesicles. The AANTs also induced intracellular autophagy and then degraded via the endolysosomal pathway. Blocking endolysosomal pathways using autophagy inhibitors prevented the degradation of AANTs through lysosomes. Our results add new insights into the pathways and mechanisms of intracellular trafficking of AANTs, and suggest that intracellular trafficking and lysosomal degradation are highly interdependent and important for efficient drug delivery, and should be evaluated together for drug carrier development.

Core-shell assay based aptasensor for sensitive and selective thrombin detection using dark-field microscopy.

In this work, we developed a robust and ultrasensitive bio-sensor based on the target-aptamer recognition strategy and microscopic enumeration of gold nanoparticles (AuNPs) using dark field microscopy (DFM). The aptasensor with a core-shell structure consisting of a magnetic bead (MB), aptamer and AuNPs was fabricated by complementary hybridization of the DNA probe on the AuNPs surface to the aptamer coupled to the MB. Upon addition of the target molecule, the strong interaction between the aptamer and the target molecule, thrombin, results in the release of the AuNPs from the MB. The quantities of thrombin is therefore linearly correlated to the number of the released AuNPs, which can be digitally counted using DFM. To demonstrate the feasible use of the aptasensor for target detection, thrombin was evaluated as the model target. The limit of detection was determined to be 2.54 fM with dynamic range of 6 fM-100 fM. When the concentration of thrombin exceeded 100 fM, the counted number of AuNPs didn't correlate linearly to molecules of thrombin anymore, as the nanoparticles aggregated partly due to high concentration. However, the color of the solution changes to purple and the concentration of free AuNPs can be conveniently quantified by UV-Vis spectroscopy for up to 100 nM. It is noteworthy that our aptasensor is very easy to operate and requires neither complex isolation and amplification processes nor expensive instruments and consumables. Furthermore, this strategy can be easily generalized to other targets by replacing the corresponding aptamers and show great potential for the detection of biomarkers in clinical samples.

Virulence genotype and phylogenetic groups in relation to Chinese herb resistance among Escherichia coli from patients with acute pyelonephritis.

BACKGROUND: Clinical isolates of herb-resistant uropathogenic E. coli were isolated. It was possible that the virulence genotypes and phylogenetic background of E. coli differed between Chinese herb-resistant E. coli and -susceptible isolates. For this purpose, the prevalence of virulence factors (VFs) and phylogenetic background, with regard to Chinese herb resistance, among E. coli strains causing acute pyelonephritis from China were investigated. MATERIALS AND METHODS: E. coli isolates from patients with acute pyelonephritis were used in this study. Standard disc diffusion methodology was used to test the susceptibility of Chinese herbal concoction against E. coli strains. Multiplex PCR amplifications employed three markers (chuA, yjaA, and TSPE4.C2) to classify E. coli isolates into one of four phylogenetic groups (group A, B1, B2, or D). The isolates were also tested for 14 virulence-associated traits (VFs) of uropathogenic E. coli. RESULTS: A total of 115 E. coli strains were isolated. 79 (68.7%) were susceptible and 36 (31.3%) were resistant to the herbal concoction. 20.9% of the isolates encoded three or more of VFs for which they were screened, with 13.9% in susceptible isolates and 36.1% in resistant isolates. The key VFs (fyuA and/or iutA siderophores) present in >80% of isolates. The papA and papC adhesins were detected in the majority of resistant isolates (72.2% and 63.9% respectively). 78.5% of susceptible isolates belong to phylogenetic groups A, while 83.3% of resistant isolates belong to group B2. CONCLUSION: PapA and papC are significant VFs with an essential role in contributing to Chinese herb-resistance. Chinese herb-resistance is associated with a shift towards more virulent strains and B2 phylogenetic group.