Gold Nanoparticle-Carrying T Cells for the Combined Immuno-Photothermal Therapy.

Cancer immunotherapy is a promising therapy to treat cancer patients with minimal toxicity, but only a small fraction of patients responded to it as a monotherapy. In this study, a strategy to boost therapeutic efficacy by combining an immunotherapy based on ex vivo expanded tumor-reactive T cells is devised, or adoptive cell therapy (ACT), with photothermal therapy (PTT). Smart gold nanoparticles (sAuNPs), which aggregates to form gold nanoclusters in the cells, are loaded into T cells, and their photothermal effects within T cells are confirmed. When transferred into tumor-bearing mice, large number of sAuNP-carrying T cells successfully infiltrate into tumor tissues and exert anti-tumor activity to suspend tumor growth, but over time tumor cells evade and regrow. Of note, ≈20% of injected doses of sAuNPs are deposited in tumor tissues, suggesting T cells are an efficient nanoparticle tumor delivery vehicle. When T cells no longer control tumor growth, PTT is performed to further eliminate tumors. In this manner, ACT and PTT are temporally coupled, and the combined immuno-photothermal treatment demonstrated significantly greater therapeutic efficacy than the monotherapy.

Investigation of artificial intelligence integrated fluorescence endoscopy image analysis with indocyanine green for interpretation of precancerous lesions in colon cancer.

Indocyanine green (ICG) has been used in clinical practice for more than 40 years and its safety and preferential accumulation in tumors has been reported for various tumor types, including colon cancer. However, reports on clinical assessments of ICG-based molecular endoscopy imaging for precancerous lesions are scarce. We determined visualization ability of ICG fluorescence endoscopy in colitis-associated colon cancer using 30 lesions from an azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model and 16 colon cancer patient tissue-samples. With a total of 60 images (optical, fluorescence) obtained during endoscopy observation of mouse colon cancer, we used deep learning network to predict four classes (Normal, Dysplasia, Adenoma, and Carcinoma) of colorectal cancer development. ICG could detect 100% of carcinoma, 90% of adenoma, and 57% of dysplasia, with little background signal at 30 min after injection via real-time fluorescence endoscopy. Correlation analysis with immunohistochemistry revealed a positive correlation of ICG with inducible nitric oxide synthase (iNOS; r > 0.5). Increased expression of iNOS resulted in increased levels of cellular nitric oxide in cancer cells compared to that in normal cells, which was related to the inhibition of drug efflux via the ABCB1 transporter down-regulation resulting in delayed retention of intracellular ICG. With artificial intelligence training, the accuracy of image classification into four classes using data sets, such as fluorescence, optical, and fluorescence/optical images was assessed. Fluorescence images obtained the highest accuracy (AUC of 0.8125) than optical and fluorescence/optical images (AUC of 0.75 and 0.6667, respectively). These findings highlight the clinical feasibility of ICG as a detector of precancerous lesions in real-time fluorescence endoscopy with artificial intelligence training and suggest that the mechanism of ICG retention in cancer cells is related to intracellular nitric oxide concentration.

Development of a Rapid LC-MS/MS Method for Simultaneous Quantification of Donepezil and Tadalafil in Rat Plasma: Its Application in a Pharmacokinetic Interaction Study after Oral Administration in Rats.

This study aimed to establish a simple and sensitive analytical method to simultaneously quantify donepezil (DPZ) and tadalafil (TAD) in rat plasma using lansoprazole (LPZ) as an internal standard (IS) by using liquid chromatography tandem mass spectrometry. The fragmentation pattern of DPZ, TAD, and IS was elucidated using multiple reaction monitoring in electrospray ionization positive ion mode for the quantification of precursor to production at m/z 380.1 → 91.2 for DPZ, m/z 390.2 → 268.1 for TAD, and m/z 370.3 → 252.0 for LPZ. The extracted DPZ and TAD from plasma using acetonitrile-induced protein precipitation was separated using Kinetex C18 (100 × 2.1 mm, 2.6 µm) column with a gradient mobile phase system consisting of 2 mM ammonium acetate and 0.1% formic acid in acetonitrile at a flow rate of 0.25 mL/min for 4 min. The selectivity, lower limit of quantification, linearity, precision, accuracy, stability, recovery, and matrix effect of this developed method was validated according to the guidelines of the U.S. Food and Drug Administration and the Ministry of Food and Drug Safety of Korea. The established method achieved acceptance criteria in all validation parameters, ensuring reliability, reproducibility, and accuracy, and was successfully implemented in a pharmacokinetic study on the co-administration of DPZ and TAD orally in rats.

A Validated Chiral LC-MS/MS Method for the Enantioselective Determination of (S)-(+)- and (R)-(-)-Ibuprofen in Dog Plasma: Its Application to a Pharmacokinetic Study.

The purpose of this study was to develop a method for simultaneously separating ibuprofen enantiomers using electrospray ionization (ESI) liquid chromatography with tandem mass spectrometry (LC-MS/MS). LC-MS/MS was operated with negative ionization and multiple reaction monitoring modes; transitions were monitored at m/z of 205.1 > 160.9 for ibuprofen enantiomers, 208.1 > 163.9 for (S)-(+)-ibuprofen-d3 [internal standard 1 (IS1)], and 253.1 > 208.9 for (S)-(+)-ketoprofen (IS2), respectively. In a one-step liquid-liquid extraction, 10 µL plasma was extracted with ethyl acetate:methyl tertiary-butyl ether of 7:3. Enantiomer chromatographic separation was carried out with an isocratic mobile phase consisting of 0.008% formic acid in water-methanol (v/v) at a flow rate of 0.4 mL/min on a CHIRALCEL® OJ-3R column (150 × 4.6 mm, 3 µm). This method was fully validated for each enantiomer and results were in compliance with the regulatory guidelines of the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. The validated assay was executed for nonclinical pharmacokinetic studies after oral and intravenous administration of racemic ibuprofen and dexibuprofen in beagle dogs.

Colloidal Porous AuAg Alloyed Nanoparticles for Enhanced Photoacoustic Imaging.

Colloidal porous AuAg alloyed nanoparticles (pAuAgNPs) were synthesized by galvanic replacement reaction from Ag nanocubes. pAuAgNPs have a 50 nm exterior diameter and half of their inner space consists of voids that have a bimodal size distribution with peaks at 21 and 8.3 nm. pAuAgNPs showed a plasmonic peak at 750 nm, which was exploited for photoacoustic (PA) imaging. Gold nanorods (AuNRs) were prepared and used as the control; they have a strong plasmonic peak at 720 nm. In in vitro experiments at respective plasmonic peak excitations, pAuAgNPs gave stronger PA signals than AuNRs by 8.9 times per particle and 11.7 times per dosage by exogenous atom. The high surface area per volume as a result of the inner voids amplified the PA signals by efficient thermoacoustic conversion. In experiments of chicken-tissue phantoms, pAuAgNPs showed PA signals through 4.5 cm thick tissue, whereas AuNRs gave no detectable signal. In whole-body in vivo experiments, pAuAgNPs injected into the body showed 2.7 times stronger PA signals than AuNRs. Coating the pAuAgNPs with a silica layer additionally increased their PA signal by 1.8 times when compared to the uncoated ones.

Reversibly pH-responsive gold nanoparticles and their applications for photothermal cancer therapy.

Microenvironment responsive nanomaterials are attractive for therapeutic applications with regional specificity. Here we report pH responsive gold nanoparticles which are designed to aggregate in acidic condition similar to cancer environment and returned to its original disassembled states in a physiological pH. The pH responsive behavior of the particles is derived by change of electrostatic interaction among the particles where attraction and repulsion play a major role in low and high pH of the environment, respectively. Since different electrostatic interaction behavior of the particles in varied pH is induced not by irreversible chemical change but by simple protonation differences, the pH responsive process of assembly and disassembly is totally reversible. The low pH specific aggregation of gold nanoparticles resulted in red shift of plasmonic absorption peak and showed higher photothermal efficacy in acidic pH than in normal physiological pH. The low pH specific photothermal effect with long wave laser irradiation was directly applied to cancer specific photothermal therapy and resulted higher therapeutic effect for melanoma cancer cells than non-pH responsive gold nanoparticles.

The association between disturbed eating behavior and socioeconomic status: the Online Korean Adolescent Panel Survey (OnKAPS).

BACKGROUND: A limited amount of research, primarily conducted in Western countries, has suggested that higher socioeconomic status (SES) is associated with higher risk of eating disorders (EDs). However, little is known about this association in Asian countries. We examined the association of SES with disturbed eating behavior (DEB) and related factors in Korean adolescents. SUBJECTS: A nationwide online panel survey was conducted in a sample of adolescents (n = 6,943, 49.9% girls). DEB was measured with the 26-item Eating Attitudes Test (EAT-26). Participants who scored ≥20 on the EAT-26 were considered to have DEB. Participants' SES was determined based on self-reported household economic status. RESULTS: The prevalence of DEB was 12.7%: 10.5% among boys and 14.8% among girls. Both boys and girls with DEB were more likely to perceive themselves as obese, experience higher levels of stress, and have lower academic achievement. The risk for DEB was significantly higher in boys of higher SES than in those of middle SES (OR = 1.45, 95%CI = 1.05-1.99 for high SES; OR = 5.16, 95%CI: 3.50-7.61 for highest SES). Among girls, higher risk of DEB was associated with the highest and lowest SES (OR = 1.52, 95%CI: 1.13-2.06 for lowest SES; OR = 2.22, 95%CI: 1.34-3.68 for highest SES). CONCLUSIONS: Despite the lower prevalence of obesity in Korea compared with Western countries, the prevalence of DEB in Korean adolescents was high, especially among girls. Moreover, the association between SES and DEB followed a U-shaped curve for girls and a J-shaped curve for boys.

Through-transmission imaging of solids in air using ultrasonic gas-jet waveguides.

An ultrasonic waveguide has been produced in air by using a gas jet. This uses the fact that a lower acoustic velocity can be produced within the jet, relative to the air surrounding it. The lower velocity is achieved by mixing carbon dioxide with air within the jet at a concentration that is a compromise between lower acoustic velocity and increasing attenuation. Using a capacitance transducer placed within the flowing gas, it is shown that improvements in the beam width can result when the gas jet is used. Air-coupled images of solid samples have been produced in through transmission, which demonstrate that an improved lateral resolution can result when a comparison is made to images from conventional air-coupled testing.