Longitudinal plasmonic detection of glucose using gold nanorods

Gold nanorod-based affinity sensors were developed utilizing concanavalin-A/dextran/glucose chemistry to detect glucose. The gold nanorods, synthesized using the seed-mediated method, were first coated with dextran sulfate. The dextran sulfate coating changed the local refractive index, which was observed as a red shift in the longitudinal plasmon band. After the addition of 8 μM concanavalin-A, gold nanorod aggregates were formed as shown by TEM analysis. The corresponding UV-Vis spectrum peak wavelength showed a red shift from 701 nm of dextran sulfate coated gold nanorods to 718 nm of concanavalin-A promoted gold nanorod aggregates. The gold nanorod aggregates were dissociated when 12 mM glucose was introduced, as illustrated by TEM images. The longitudinal plasmon resonance of the UV-Vis spectrum also showed a blue shift from 718 nm of dextran sulfate-coated gold nanorods associated by concanavalin-A to 714 nm of dissociated dextran sulfate-coated gold nanorods. The degree of the spectrum peak wavelength shift of the dextran sulfate-coated gold nanorods associated by concanavalin-A can be modulated using glucose ranging from 1 to 30 mM

Anti-neuroblastoma activity of gold nanorods bound with GD2 monoclonal antibody under near-infrared laser irradiation

High-risk neuroblastoma is one of the most common deaths in pediatric oncology. Current treatment of this disease involves a coordinated sequence of chemotherapy, surgery, and radiation. Further advances in therapy will require the targeting of tumor cells in a more selective and efficient way so that survival can be improved without substantially increasing toxicity. To achieve tumor-selective delivery, disialoganglioside (GD2) expressed by almost all neuroblastoma tumors represents a potential molecular target that can be exploited for tumor-selective delivery. In this study, GD2 monoclonal antibody (anti-GD2) was conjugated to gold nanorods (GNRs) which are one of anisotropic nanomaterials that can absorb near-infrared (NIR) laser light and convert it to energy for photothermolysis of tumor cells. Thiolated chitosan, due to its biocompatibility, was used to replace cetyltrimethylammonium bromide (CTAB) originally used in the synthesis of gold nanorods. In order to specifically target GD2 overexpressed on the surface of neuroblastoma stNB-V1 cells, anti-GD2 was conjugated to chitosan modified GNRs (CGNRs). To examine the fate of CGNRs conjugated with anti-GD2 after incubation with neuroblastoma cells, rhadoamine B was labeled on CGNRs functionalized with anti-GD2. Our results illustrated that anti-GD2-conjugated CGNRs were extensively endocytosed by GD2+ stNB-V1 neuroblastoma cells via antibody-mediated endocytosis. In addition, we showed that anti-GD2 bound CGNRs were not internalized by GD2– SH-SY5Y neuroblastoma cells. After anti-GD2-linked CGNRs were incubated with neuroblatoma cells for six hours, the treated cells were further irradiated with 808 nm NIR laser. Post-NIR laser exposure, when examined by calcein-AM dye, stNB-V1 cells all underwent necrosis, while non-GD2 expressing SH-SY5Y cells all remained viable. Based on the in vitro study, CGNRs bound with anti-GD2 has the potential to be utilized as a therapeutic thermal coupling agent that generates heat sufficient to selectively kill neuroblastoma cells under NIR laser light exposure

Ring-Opening Polymerization of ε-Caprolactone initiated by Ganciclovir (GCV) for the preparation of GCV-tagged polymeric micelles

Ganciclovir (GCV) is a nucleoside analogue with antiviral activity against herpes viral infections, and the most widely used antiviral to treat cytomegalovirus infections. However, the low bioavailability and short half-life of GCV necessitate the development of a carrier for sustained delivery. In this study, guanosine-based GCV was used as the initiator directly in ring-opening polymerization of ε-caprolactone (ε-CL) to form hydrophobic GCV-poly(caprolactone) (GCV-PCL) which was then grafted with hydrophilic chitosan to form amphiphilic copolymers for the preparation of stable micellar nanoparticles. Successful synthesis of GCV-PCL and GCV-PCL-chitosan were verified by 1H-NMR analysis. Self-assembled micellar nanoparticles were characterized by dynamic light scattering and zetasizer with an average size of 117 nm and a positive charge of 24.2 mV. The drug release kinetics of GCV was investigated and cytotoxicity assay demonstrated that GCV-tagged polymeric micelles were non-toxic. Our results showed that GCV could be used directly in the initiation of ring-opening polymerization of ε-CL and non-toxic polymeric micelles for GCV delivery can be formed

Polymeric Nanovectors Incorporated with Ganciclovir and HSV-tk Encoding Plasmid for Gene-Directed Enzyme Prodrug Therapy

In the area of gene-directed enzyme prodrug therapy (GDEPT), using herpes simplex virus thymidine kinase (HSV-tk) paired with prodrug ganciclovir (GCV) for cancer treatment has been extensively studied. It is a process involved with two steps whereby the gene (HSV-tk) is first delivered to malignant cells. Afterward, non-toxic GCV is administered to that site and activated to cytotoxic ganciclovir triphosphate by HSV-tk enzyme expressed exogenously. In this study, we presented a one-step approach that both gene and prodrug were delivered at the same time by incorporating them with polymeric micellar nanovectors. GCV was employed as an initiator in the ring-opening polymerization of ε-caprolactone (ε-CL) to synthesize hydrophobic GCV-poly(caprolactone) (GCV-PCL), which was furthered grafted with hydrophilic chitosan to obtain amphiphilic polymer (GCV-PCL-chitosan) for the fabrication of self-assembled micellar nanoparticles. The synthesized amphiphilic polymer was characterized using Fourier transform infrared spectroscopy and proton nuclear magnetic resonance. Micellar prodrug nanoparticles were analyzed by dynamic light scattering, zeta potential, critical micelle concentration, and transmission electron microscopy. Polymeric prodrug micelles with optimal features incorporated with HSV-tk encoding plasmids were cultivated with HT29 colorectal cancer cells and anticancer effectiveness was determined. Our results showed that prodrug GCV and HSV-tk cDNA encoded plasmid incorporated in GCV-PCL-chitosan polymeric nanocarriers could be delivered in a one-step manner to HT-29 cells and triggered high cytotoxicity

Enhanced anticancer activity of 5\u27-DFUR-PCL-MPEG polymeric prodrug micelles encapsulating chemotherapeutic drugs

The compound 5’-deoxy-5-fluorouridine (5’-DFUR) is a prodrug of the anti-tumor drug 5-fluorouracil (5-FU). Thymidine phosphorylase (TP) is an enzyme that can convert 5’-DFUR to its active form 5-FU and the expression of TP is upregulated in various cancer cells. In this study, 5’-DFUR associated with amphiphilic copolymer poly(ε-caprolactone)-methoxy poly(ethylene glycol) (5’-DFUR-PCL-MPEG) was synthesized, characterized, and self-assembled into functional polymeric micelles. To demonstrate that the prodrug 5’-DFUR could convert into cytotoxic 5-fluorouracil (5-FU) by endogenous TP, HT-29 colorectal cancer cells were treated with 5’-DFUR-PCL-MPEG polymeric micelles for various time periods. Chemotherapeutic drugs doxorubicin (DOX) and 7-ethyl-10-hydroxycamptothecin (SN-38) were also encapsulated separately into 5’-DFUR-PCL-MPEG polymeric micelles to create a dual drug-loaded system. HT-29 cells were treated with DOX or SN-38 encapsulated 5’-DFUR-PCL-MPEG polymeric micelles to examine the efficacy of dual drug-loaded micelles. As a result, HT-29 cells treated with 5’-DFUR-PCL-MPEG polymeric micelles showed up to 40% cell death rate after a 72-h treatment. In contrast, HT-29 cells challenged with DOX or SN-38 encapsulated 5’-DFUR-incorporated polymeric micelles showed 36% and 31% in cell viability after a 72-h treatment, respectively

Begonia wuzhishanensis (sect. Diploclinium, Begoniaceae), a new species from Hainan Island, China

Background: Hainan is the largest island of the Indo-Burma Biodiversity Hotspot and has the best preserved and most extensive tropical forests in China. A recent study on distribution of endangered species in China identifies southern Hainan as one of eight hotspots for plant conservation in the country. In continuation of our studies of Asian Begonia, we report the discovery of an attractive undescribed species, B. wuzhishanensis C.-I Peng, X.H. Jin & S.M.Ku, from Hainan Island. Results: Living plant of the new species, Begonia wuzhishanensis, was collected in 2009 and cultivated in the experimental greenhouse for morphological and cytological studies. It flowered consecutively in 2012 and 2013 in the experimental greenhouse, Academia Sinica. It was assigned to the large, heterogeneous sect. Diploclinium. The chromosome number of this new species was determined to be 2n = 26. Conclusions: A careful study of literature, herbarium specimens and living plants, both in the wild and in cultivation, support the recognition of the new species Begonia wuzhishanensis, which is described in this paper. Begonia wuzhishanensis is currently known only from Fanyang, Wuzhishan Mountain in the center of the island. A line drawing, color plate, and a distribution map are provided to aid in identification

Endoscopic Balloon Dilatation for Esophageal Strictures in Children Younger Than 6 Years: Experience in a Medical Center

Esophageal strictures in children may be caused by congenital anomaly, caustic agent or foreign body ingestion, complication of reflux esophagitis, and after esophageal surgery. Accidental ingestion of alkaline fluid is the most common cause of corrosive esophagitis in children in Taiwan. In this article, we studied 10 pediatric patients who had esophageal strictures and required endoscopic balloon dilatation (EBD) therapy under general anesthesia from January 2003 to June 2009. The median age of the studied children who received their first EBD treatment was 36.2 months (13.4–60.9 months), with a dilator size of 8.0mm (5–12 mm). The interval between injury and initial EBD was 3.0 months (1.3–60.8 months). The treatment duration averaged 16.7 months (3.0–69.3 months), with 13.5 (4–31) instances of EBD therapy per patient. The greater the length of stricture, the more number of times EBD was needed. In these cases, no severe complication was found after the procedure. The result indicated that EBD under general anesthesia was a safe and effective method to resolve the symptom of dysphagia and diet condition. Because of the limited number of study cases, long-term studies are required to further confirm the clinical effect of EBD under general anesthesia

Efficacy of multidomain interventions to improve physical frailty, depression and cognition: data from cluster- randomized controlled trials

BackgroundFrailty is the pre- eminent exigency of aging. Although frailty- related impairments are preventable, and multidomain interventions appear more effective than unimodal ones, the optimal components remain uncertain.MethodsWe devised multidomain interventions against physical and cognitive decline among prefrail/frail community- dwelling - ¥65- year- olds and evaluated these in complementary cluster- randomized trials of efficacy and participant empowerment. The Efficacy Study compared ~3- monthly telephone consultations vs. 16, 2 h sessions/year comprising communally partaken physical and cognitive training plus nutrition and disease education; the Empowerment Study compared the standard Efficacy Study multidomain intervention (Sessions 1- 10) vs. an enhanced version redesigned to empower and motivate individual participants. Changes from baseline in physical, functional, and cognitive performance were measured after 6 and 12 months in the Efficacy Study and after 6 months in the Empowerment Study, with post- intervention follow- up at 9 months. Primary outcomes are as follows: Cardiovascular Health Study frailty score; gait speed; handgrip strength; and Montreal Cognitive Assessment (MoCA). Secondary outcomes are as follows: instrumental activities of daily living; metabolic equivalent of task (MET); depressed mood (Geriatric Depression Scale- 5 - ¥2); and malnutrition (Mini- Nutritional Assessment short- form - ¤11). Intervention effects were analyzed using a generalized linear mixed model.ResultsEfficacy Study participants (n = 1082, 40 clusters) were 75.1 ± 6.3 years old, 68.7% women, and 64.7% prefrail/frail; analytic clusters: 19 intervention (410/549 completed) vs. 21 control (375/533 completed). Empowerment Study participants (n = 440, 14 clusters) were 75.9 ± 7.1 years old, 83.6% women, and 56.7% prefrail/frail; analytic clusters: seven intervention (209/230 completed) vs. seven control (189/210 completed). The standard and enhanced multidomain interventions both reduced frailty and significantly improved aspects of physical, functional, and cognitive performance, especially among - ¥75- year- olds. Standard multidomain intervention decreased depression [odds ratio 0.56, 95% confidence interval (CI) 0.32, 0.99] and malnutrition (odds ratio 0.45, 95% CI 0.26, 0.78) by 12 months and improved concentration at Months 6 (0.23, 95% CI 0.04, 0.42) and 12 (0.46, 95% CI 0.22, 0.70). Participant empowerment augmented activity (4.67 MET/h, 95% CI 1.64, 7.69) and gait speed (0.06 m/s, 95% CI 0.00, 0.11) at 6 months, with sustained improvements in delayed recall (0.63, 95% CI 0.20, 1.06) and MoCA performance (1.29, 95% CI 0.54, 2.03), and less prevalent malnutrition (odds ratio 0.39, 95% CI 0.18, 0.84), 3 months after the intervention ceased.ConclusionsPragmatic multidomain intervention can diminish physical frailty, malnutrition, and depression and enhance cognitive performance among community- dwelling elders, especially - ¥75- year- olds; this might supplement healthy aging policies, probably more effectively if participants are empowered.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/1/jcsm12534.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/2/10.1002_jcsm.12534_Fig_S4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/3/jcsm12534_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/4/10.1002_jcsm.12534_Fig_S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/5/10.1002_jcsm.12534_Table_S3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/6/10.1002_jcsm.12534_Fig_S3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/7/10.1002_jcsm.12534_Appendix_S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/8/10.1002_jcsm.12534_Table_S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/9/10.1002_jcsm.12534_Table_S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/10/10.1002_jcsm.12534_Fig_S1.pd