New insight on optical and magnetic Fe3O4 nanoclusters promising for near infrared theranostic applications.

Extensive efforts have been devoted to the development of a new biophotonic system using near infrared (NIR) nano-agents for non-invasive cancer diagnosis and therapy. Here, we developed a simple synthesis reaction of ligands, hydrazine, and iron(ii) chloride to fabricate Fe3O4 cluster-structured nanoparticles (CNPs) with interesting NIR photonics and high magnetization (Ms: 98.3 emu g(-1) and proton relaxivity r2: 234.6 mM(-1) s(-1)). These Fe3O4 CNPs exhibited optical absorption and reflection over all wavelengths, showing a U-shape absorption band with a low absorbance at a range of 750-950 nm and a progressive evolution in the second near infrared region. Strengthening of the scattering effect by incubating Fe3O4 CNPs with HeLa cells was observed when optical contrast enhancement was performed in an optical coherence tomography (OCT) microscope system with a laser light source at 860 nm. Using a 1064 nm laser at a low power density (380 mW cm(-2)) to excite the Fe3O4 CNPs (375 ppm[Fe]) led to a rise in the water temperature from 25 °C to 58 °C within 10 min. Finally, we present the first example of magnetomotive OCT cellular imaging combined with enhanced photothermal therapy using Fe3O4 CNPs and applying a magnetic field, which is promising for preclinical and clinical trials in the future.

Enhanced Raman sensitivity and magnetic separation for urolithiasis detection using phosphonic acid-terminated Fe3O4 nanoclusters.

Surface-functionalized Fe3O4 nanoparticles are emerging as promising agents for the selective and magnetic separation of various biological molecules. In principle, by engineering the surface of Fe3O4 nanoparticles, they can be applied as tracers to seek and recognize metabolites and secretions of specific diseases. In this report, we developed Fe3O4 nanoclusters with high magnetization and an amino-functionalized surface via the reaction between FeCl2, a hydrazine reductant, and a gelatin polymer to demonstrate magnetically separated prevalent urinary crystals. The surface of the gelatin-coated Fe3O4 nanoclusters was modified by using aminopropylphosphonic acid by amine coupling using EDC and NHS, which led to the exposure of their phosphonic acid groups and improved their affinity for fine Ca-based urinary crystals in the patient's urine. By subjecting the Fe3O4 nanoclusters that were bound to urinary crystals to Raman spectroscopy analysis, the crystalline types of the pre-concentrated urinary components were easily identified. The assignment of the vibration peaks of the crystals is promising for eliminating the false positives that occur when using a microscopic analysis method for urine crystal diagnosis. Sample preparation and identification required less than 10 min. Finally, we demonstrated that this non-invasive analytic platform exhibits a rapid and efficient detection rate of single- and multi-component urinary crystals from urine metabolites. A good correlation (86%) was observed between this non-invasive analytic platform and the diagnostic reports from 35 urolithiasis patients. We expect that this Fe3O4 nanocluster integrated Raman spectrum method will provide crystal information that could help early management for urolithiasis patients.

Development of therapeutic Au-methylene blue nanoparticles for targeted photodynamic therapy of cervical cancer cells.

Photodynamic therapy (PDT) involves the cellular uptake of a photosensitizer (PS) combined with oxygen molecules and light at a specific wavelength to be able to trigger cancer cell death via the apoptosis pathway, which is less harmful and has less inflammatory side effect than necrosis. However, the traditional PDT treatment has two main deficiencies: the dark toxicity of the PS and the poor selectivity of the cellular uptake of PS between the target cells and normal tissues. In this work, methylene blue (MB), a known effective PS, combined with Au nanoparticles (NPs) was prepared using an intermolecular interaction between a polystyrene-alt-maleic acid (PSMA) layer on the Au NPs and MB. The Au@polymer/MB NPs produced a high quantum yield of singlet oxygen molecules, over 50% as much as that of free MB, when they were excited by a dark red light source at 660 nm, but without significant dark toxicity. Furthermore, transferrin (Tf) was conjugated on the Au@polymer/MB NPs via an EDC/NHS reaction to enhance the selectivity to HeLa cells compared to 3T3 fibroblasts. With a hand-held single laser treatment (32 mW/cm) for 4 min, the new Au@polymer/MB-Tf NPs showed a 2-fold enhancement of PDT efficiency toward HeLa cells over the use of free MB at 4 times dosage. Cellular staining examinations showed that the HeLa cells reacted with Au@polymer/MB-Tf NPs and the 660 nm light excitation triggered PDT, which caused the cells to undergo apoptosis ("programmed" cell death). We propose that applying this therapeutic Au@polymer/MB-Tf nanoagent is facile and safe for delivery and cancer cell targeting to simultaneously minimize side effects and accomplish a significant enhancement in photodynamic therapeutic efficiency toward next-generation nanomedicine development.

Parallel second stent placement for refractory ureteral stent malfunction in malignant ureteral obstruction.

PURPOSE: To review retrospectively the outcome of placement of a parallel second ureteral stent in patients with urinary obstruction secondary to a malignancy. MATERIALS AND METHODS: During the period 2005-2008, the medical records of patients with ureteral obstruction from an abdominal malignancy were reviewed. Patients who experienced malfunction of the first ureteral stent subsequently underwent either initial stent exchange (control group) or a parallel second ureteral stent placement. The outcomes of both groups were evaluated in terms of stent function at 1 week, 1 month, and 3 months after the procedure. Several clinical and imaging parameters were also compared between the two groups. RESULTS: The stent malfunction rate increased more rapidly in the control group. In 1 week, the malfunction rate was 29.4% in the parallel ureteral stent group and 56.7% in the control group. By the end of the third month, the malfunction rate was 72.7% in the parallel ureteral stent group and 100% in the control group. The creatinine level after the procedure was significantly lower in the parallel ureteral stent group (P = 0.004). The incidence of symptomatic urinary tract infection (UTI) was around 30% in both groups (P = 1.000). CONCLUSIONS: Parallel second ureteral stent placement has a high technical success rate. For terminally ill patients who have a malignancy and an occluded ureteral stent, the technique can effectively relieve obstruction and prolong the function of the stent.

Multidrug-resistant Acinetobacter baumannii isolates in pediatric patients of a university hospital in Taiwan.

BACKGROUND AND PURPOSE: Acinetobacter baumannii is one of the common nosocomial pathogens, and the emergence of multidrug-resistant A. baumannii (MDRAB) is a therapeutic problem. We describe the clinical characteristics and outcomes of MDRAB colonization/infection in pediatric patients at the National Taiwan University Hospital. METHODS: Fifty two pediatric patients with 205 MDRAB isolates collected between April 2000 and December 2005 were included for investigation of their clinical characters, presentations, and outcome. RESULTS: Among these 205 isolates, 20 (9.8%) were from sterile body sites (11 from blood, 8 from catheter tips, and 1 from ascites), 154 (75.1%) from respiratory sites, 18 (8.8%) from skin or wound pus, 5 (2.4%) from urine, and 8 (3.9%) from other sites. The mean age was 6 years. The common underlying diseases were haematological or oncological diseases (n = 15, 28.8%), neonatal disorders (6, 11.5%), cyanotic congenital heart diseases (10, 19.2%), neurology disorders (12, 23.1%), and gastrointestinal tract disorders (3, 5.8%). Seventeen patients (32.7%) had received major surgery, and 48 (92.3%) had used ventilators. Fourteen patients (26.9%) had neutropenia and 46 (88.5%) had used broad-spectrum antibiotics. There were 31 patients (59.6%) with suspected or proven MDRAB infections, including sepsis (9 patients), pneumonia (19), wound infections (3), urinary tract infections (2), peritonitis (1), and perineal infection (1). Seven (77.8%) of the 9 sepsis patients died. The overall mortality rate was 42.3% (22 cases). CONCLUSIONS: The threat of MDRAB has been recognized in our hospital for several years. Host defense deficiencies, prolonged intensive care unit hospitalizations, and prior broad-spectrum antibiotic use play a major role in MDRAB infection and colonization.