Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells

Single-walled carbon nanotubes (SWNTs) have been identified as an efficient drug carrier. Here a controlled drug-delivery system based on SWNTs coated with doxorubicin (DOX) through hydrazone bonds was developed, because the hydrazone bond is more sensitive to tumor microenvironments than other covalent linkers. The SWNTs were firstly stabilized with polyethylene glycol (H2N-PEG-NH2). Hydrazinobenzoic acid (HBA) was then covalently attached on SWNTs via carbodiimide-activated coupling reaction to form hydrazine-modified SWNTs. The anticancer drug DOX was conjugated to the HBA segments of SWNT using hydrazine as the linker. The resulting hydrazone bonds formed between the DOX molecules and the HBA segments of SWNTs are acid cleavable, thereby providing a strong pH-responsive drug release, which may facilitate effective DOX release near the acidic tumor microenvironment and thus reduce its overall systemic toxicity. The DOX-loaded SWNTs were efficiently taken up by HepG2 tumor cells, and DOX was released intracellularly, as revealed by MTT assay and confocal microscope observations. Compared with SWNT-DOX conjugate formed by supramolecular interaction, the SWNT-HBA-DOX featured high weight loading and prolonged release of DOX, and thus improved its cytotoxicity against cancer cells. This study suggests that while SWNTs have great potential as a drug carrier, the efficient formulation strategy requires further study

Nanotherapeutics in angiogenesis: synthesis and in vivo assessment of drug efficacy and biocompatibility in zebrafish embryos

Author name used in this publication: Wong, Wing-Tak.published_fina

Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared with metformin: A population-based cohort study

Background Commonly prescribed diabetic medications such as metformin and sulfonylurea may be associated with different arrhythmogenic risks. This study compared the risk of ventricular arrhythmia or sudden cardiac death between metformin and sulfonylurea users in patients with type 2 diabetes. Methods and Results Patients aged ≥40 years who were diagnosed with type 2 diabetes or prescribed antidiabetic agents in Hong Kong between January 1, 2009, and December 31, 2009, were included and followed up until December 31, 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of ventricular arrhythmia or sudden cardiac death. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. The matched cohort consisted of 16 596 metformin users (47.70% men; age, 68±11 years; mean follow‐up, 4.92±2.55 years) and 16 596 sulfonylurea users (49.80% men; age, 70±11 years; mean follow‐up, 4.93±2.55 years). Sulfonylurea was associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin hazard ratio (HR, 1.90 [95% CI, 1.73–2.08]). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease. Conclusions Sulfonylurea use is associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin in patients with type 2 diabetes

Isostructural second-order phase transition of b-Bi2O3 at high pressures: an experimental and theoretical study

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Physical Chemistry C, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jp507826jWe report a joint experimental and theoretical study of the structural and vibrational properties of synthetic sphaerobismoite (beta-Bi2O3) at high pressures in which room-temperature angle-dispersive X-ray diffraction (XRD) and Raman scattering measurements have been complemented with ab initio total energy and lattice dynamics calculations. Striking changes in Raman spectra were observed around 2 GPa, whereas X-ray diffraction measurements evidence no change in the tetragonal symmetry of the compound up to 20 GPa; however, a significant change exists in the compressibility when increasing pressure above 2 GPa. These features have been understood by means of theoretical calculations, which show that beta-Bi2O3 undergoes a pressure-induced isostructural phase transition near 2 GPa. In the new isostructural beta' phase, the Bi3+ and O2- environments become more regular than those in the original beta phase because of the strong decrease in the activity of the lone electron pair of Bi above 2 GPa. Raman measurements and theoretical calculations provide evidence of the second-order nature of the pressure-induced isostructural transition. Above 20 GPa, XRD measurements suggest a partial amorphization of the sample despite Raman measurements still show weak peaks, probably related to a new unknown phase which remains up to 27 GPa. On pressure release, XRD patterns and Raman spectra below 2 GPa correspond to elemental Bi-I, thus evidencing a pressure-induced decomposition of the sample during downstroke.Financial support from the Spanish Consolider Ingenio 2010 Program (MALTA Project CSD2007-00045) is acknowledged. This work was also supported by Brazilian Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) under Project 201050/2012-9, Spanish MICINN under Projects MAT2010-21270-004-01/03/04 and MAT2013-46649-C4-2/3/4-P, Spanish MINECO under Project CTQ2012-36253-C03-02, and from Vicerrectorado de Investigacion de la Universitat Politecnica de Valencia under Projects UPV2011-0914 PAID-05-11 and UPV2011-0966 PAID-06-11. Supercomputer time has been provided by the Red Espanola de Supercomputacion (RES) and the MALTA cluster. JAS. acknowledges Juan de la Cierva fellowship program for financial support.Pereira, ALJ.; Sans Tresserras, JÁ.; Vilaplana Cerda, RI.; Gomis, O.; Manjón Herrera, FJ.; Rodriguez-Hernandez, P.; Muñoz, A.... (2014). Isostructural second-order phase transition of b-Bi2O3 at high pressures: an experimental and theoretical study. Journal of Physical Chemistry C. 118(40):23189-23201. https://doi.org/10.1021/jp507826jS23189232011184

Exogenous carbon monoxide suppresses adaptive response induced in zebrafish embryos in vivo by microbeam protons

Dechorionated embryos of the zebrafish, Danio rerio, irradiated at 5 h post-fertilization (hpf) with 30 protons delivered to 10 separate positions each with an energy of 3.4 MeV from the microbeam irradiation facility (Single-Particle Irradiation System to Cell, acronym as SPICE) at the National Institute of Radiological Sciences (NIRS), developed radioadaptive response (RAR) against a subsequent challenging exposure of 2 Gy of X-ray irradiation at 10 hpf, corroborated by reduced apoptotic signals at 25 hpf revealed through terminal dUTP transferase-mediated nick end-labeling assay. \nThe effects of the CO liberator tricarbonylchloro(glycinato)ruthenium (II) (CORM-3) on the induction of RAR were examined by transferring the irradiated embryos to freshly prepared medium with the chemical at different time points after the application of the priming dose. Our results showed that transfer of irradiated embryos into media with CORM-3 at 0, 1, 2 and 3 h after application of priming exposure significantly suppressed RAR, while transfer at 5 h did not suppress RAR. This was attributed to the protection of bystander cells from the released CO, which caused less de novo synthesis of factors and thus less efficient induction of RAR. Once the factors were synthesized, RAR was induced, which would not be further affected by the application of CORM-3 introduced at 5 h after the application of the priming dose

Roles of nitric oxide in adaptive response induced in zebrafish embryos in vivo by microbeam protons

Radioadaptive response (RAR) was successfully induced in dechorionated (5 h post-fertilization, hpf) embryos of the zebrafish, Danio rerio, by 3.4 MeV protons from the microbeam irradiation facility (Single-Particle Irradiation System to Cell, acronym as SPICE) [ 1] at the National Institute of Radiological Sciences (NIRS), against a challenging exposure of 2 Gy of X-ray irradiation at 10 hpf. The RAR induction was corroborated by reduced apoptotic signals at 25 hpf revealed through terminal dUTP transferase-mediated nick end-labeling assay. If de novo synthesis of factors was required for RAR induction, these should have already been synthesized at 5 h after the priming dose. \nApplication of a nitric oxide scavenger 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) to the medium at 0, 1, 2, 3 or 5 h after application of priming exposure significantly suppressed RAR. The suppression of RAR with the application of cPTIO to the medium at 5 h after the priming dose irradiation, where de novo synthesis of factors should have been completed, suggested that NO scavenging impaired the repair machineries in the bystander cells. The suppression of RAR with the application of cPTIO to the medium at earlier than 5 h after the priming dose irradiation could be explained by the scavenging of bystander NO signals in the medium and thus deterring the de novo synthesis of factors