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RSC Advances · 2015 ·Vol. 5 ·期 111 ·91398-91406 · IF 3.84

Single and repeated dose toxicity of citric acid-based carbon dots and a derivative in mice

Xiao Zheng,Dan Shao,Jing Li,Yubin Song,Yujing Chen,Yue Pan,Shoujun Zhu,Bai Yang,Li Chen

Carbon dots (CDs) have recently emerged as a new class of fluorescent nanomaterials and are already competitive in many respects to conventional semiconductor quantum dots (QDs). Despite CDs remarkable advantages in bioimaging, biosensing and other biomedical applications, their biosafety is still unclear. In the present study, the systematic single and repeated dose toxicity and biodistribution of two citric acid-based probes (CDs and a derivative, Et-IPCA) were investigated in vivo. For the single dose toxicity studies, the lethal dose 50 (LD50) of CDs was 391.615 mg kg−1 and 357.771 mg kg−1 for female and male mice, respectively, while Et-IPCA reached its saturation point in solution at 25 mg kg−1 and did not lead to the death of any mice at that concentration. For the repeated dose toxicity studies, although there were temporary changes in hematological parameters suggesting an acute inflammatory response after seven doses, the data on the body weight, organ coefficients, hematological parameters, blood biochemistry, and organ histopathology at the end of the 90 day recovery period suggested that both the CDs and Et-IPCA had low toxicity over the 90 day period. These findings will be useful for the future development of CDs-based drug delivery systems and for the development of clinical applications of these systems.

CAS / MDL: 77-92-9 5949-29-1
研究领域: 生物医学 · 毒理学 · 纳米材料科学
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POLYMERS FOR ADVANCED TECHNOLOGIES · 2020 ·Vol. 31 ·期 10 ·2127-2135 · IF 2.578

Preparation of W1/O/W2 emulsion to limit the diffusion of Fe3+ in the Fricke gel 3D dosimeter

Wei Zhang,Kaikai Wang,Xiaodan Hu,Xiaohong Zhang,Shuquan Chang,Haiqian Zhang

The irradiation of tumors in radiotherapy requires accurate 3D dosimetry. The Fricke 3D dosimeters, which were considered to be high potential of application in 3D dosimetry, suffer from a reduced temporal integrity of dose distribution caused by Fe 3+ ions diffusion. To overcome the drawback, we firstly synthesized a kind of amphiphilic molecules with critical micelle concentration of 0.45 g/L and hydrophile-lipophile balance value of 10, then prepared multiple emulsions by self-assembling those molecules in Fricke solution under liquid paraffin, and finally obtained Fricke hydrogel embedded with the multiple emulsions. The diffusion coefficient of Fe 3+ ions in the embedded Fricke hydrogel was measured to be 0.17 mm 2 /h. The hydrogel dosimeter exhibits considerable potential for use in dose verification applications.

CAS / MDL: 78-67-1 36405-47-7
研究领域: 放射肿瘤学 · 医学物理 · 剂量学 · 材料科学
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Clinical Pharmacology in Drug Development · 2020 ·Vol. 10 ·期 1 ·57-67 · IF 1.903

Effects of ABCB1, UGT1A1, and UGT1A9 Genetic Polymorphisms on the Pharmacokinetics of Sitafloxacin Granules in Healthy Subjects

Lu-Ning Sun,Guo-Xian Sun,Yu-Qing Yang,Ye Shen,Feng-Ru Huang,Li-Jun Xie,Juan Cheng,Hong-Wen Zhang,Xue-Hui Zhang,Yun Liu,Yong-Qing Wang

Sitafloxacin, a new fluoroquinolone, has strong antibacterial activity. We evaluated the effects of sitafloxacin granules in single-dose and multidose cohorts and the effects of ABCB1, UGT1A1 , and UGT1A9 genetic polymorphisms on the pharmacokinetics (PK) of sitafloxacin in healthy subjects. The single-dose study included 3 fasted cohorts receiving 50, 100, and 200 mg of sitafloxacin granules and 1 cohort receiving 50 mg of sitafloxacin granules with a high-fat meal. The multidose study included 1 cohort receiving 100 mg of sitafloxacin granules once daily for 5 days. PK parameters were calculated using noncompartmental parameters based on concentration-time data. The genotypes for ABCB1 , UGT1A1 , and UGT1A9 single-nucleotide polymorphisms were determined using Sanger sequencing. Subsequently, the association between sitafloxacin PK parameters and target single-nucleotide polymorphisms was analyzed. Sitafloxacin granules were well tolerated up to 200 and 100 mg in the single-dose and multidose studies, respectively. Sitafloxacin AUC and C max increased linearly within the detection range, and a steady state was reached within 3 days after the administration of multiple oral doses. Our findings showed that C max was lower in the ABCB1 (rs1045642) mutation group, whereas t 1/2 was longer in the UGT1A1 (rs2741049) and UGT1A9 (rs3832043) mutation groups. In conclusion, sitafloxacin granules were safe at single doses and multiple doses up to 200 and 100 mg/day, respectively, with a linear plasma PK profile. However, ABCB1 (rs1045642), UGT1A1 (rs2741049), and UGT1A9 (rs3832043) genetic polymorphisms are likely to influence the C max or t 1/2 and thereby merit further clinical evaluation.

研究领域: 药理学 · 遗传学 · 临床研究
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POLYMERS FOR ADVANCED TECHNOLOGIES · 2022 ·Vol. 34 ·期 2 ·539-548 · IF 3.348

Radiation-sensitive nanogel-incorporated Fricke hydrogel dosimeters with reduced diffusion rates

Kaikai Wang,Wei Zhang,Yameng Qi,Xiaodan Hu,Xiaohong Zhang,Shuquan Chang,Haiqian Zhang

Fricke gel dosimeters have great potential for three-dimensional (3D) dose verification in radiation therapy; however, they suffer from time-dependent ion diffusion after irradiation, severely affecting their stability and reliability. In this work, a pullulan-based amphiphilic molecule was synthesized, characterized, and self-assembled into nanogels. Nanogel structures were embedded into gel dosimeters to reduce the diffusion rates, and radiation-sensitive nanogel-incorporated Fricke hydrogel nanocomposites were prepared successfully. The results demonstrated that the diffusion coefficient of improved dosimeters was reduced to 0.125 ± 0.001 mm 2 h −1 , while maintaining the high optical dose sensitivity (0.0410 ± 0.0004 Gy −1 cm −1 ). It provides a powerful tool toward the practical application of 3D dosimeters.

研究领域: 放射治疗 · 材料科学 · 医学物理
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Materials Horizons · 2024 · IF 12.2

High-resolution 3D Radiochromic Hydrogel Photonic Crystal Dosimeter for Clinical Radiotherapy

Zhihao Wang,Xianmei Chen,Tingting Wang,Mingshuo Tang,Zhiwei He,Yunlong Wang,Jun Ma

The precise, rapid and direct visualization of 3D topographical dose in the target tissue that is crucial for effective radiation therapy remains a challenge. Herein, by combining hydrogel photonic crystals with film stacking or 3D printing, a 3D radiochromic dosimeter with a dose sensitivity up to 10 nm/Gy, a spatial resolution < 50 μm, and the ability to detect complex 3D topographical dose distribution was proposed for clinical radiation dose verification. The performance of the dosimeter by radiation-induced polymer cross-linking and consequent Bragg wavelength shift can be tuned via the solid content and extent of acrylate modification. The combination of rapid readout, low dose response, high spatial resolution, and good environmental stability highlights the translational potential of this technology for topographical dose mapping in clinical radiotherapy applications.

研究领域: 医学物理 · 放射肿瘤学 · 生物医学工程
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PLoS One · 2020 ·Vol. 15 ·期 3 ·e0230410 · IF 2.74

Improvement in sensitivity of radiochromic 3D dosimeter based on rigid polyurethane resin by incorporating tartrazine

Jin Dong Cho,Jaeman Son,Chang Heon Choi,Jin Sung Kim,Hong-Gyun Wu,Jong Min Park,Jung-in Kim

We investigated the influence of incorporating tartrazine on the dose response characteristics of radiochromic 3D dosimeters based on polyurethane resin. We use three types of polyurethane resins with different Shore hardness values: 30 A, 50 A, and 80 D. PRESAGE dosimeters are fabricated with different chemical components and concentrations. Tartrazine (Yellow No. 5) helps incorporate a yellow dye to fabricate the dosimeter. Elemental composition is analyzed with the Z eff . Three sets of six different PRESAGE dosimeters were fabricated to investigate the effects of incorporating yellow dye on the dose response characteristics of the dosimeter. The dose response curve was obtained by measuring the optical absorbance using a spectrometer and optical density using optical CT, respectively. The energy and dose rate dependences are evaluated for the dosimeter with the highest sensitivity. For the optical density measurement, significant sensitivity enhancements of 36.6% and 32.7% were achieved in polyurethane having a high Shore hardness of 80 D and 50 A by incorporating tartrazine, respectively. The same results were obtained in the optical absorbance measurements. The ratio of the Z eff of the dosimeter with 80 D Shore hardness to water was 1.49. The polyurethane radiochromic dosimeter with a Shore hardness of 80 D showed the highest sensitivity and energy and dose rate independence upon the incorporation of tartrazine.

CAS / MDL: 129-73-7 558-13-4
研究领域: 医学物理 · 放射生物学
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E-POLYMERS · 2021 ·Vol. 21 ·期 1 ·616-624 · IF 2.025

Rare-earth doped radioluminescent hydrogel as a potential phantom material for 3D gel dosimeter

Tao Yang,Junhui Wang,Jiali Tu,Xiaoxi Zhou,Jiamin Sun,Jian Chen,Wanxin Wen,Yanfei Wang

Cancer prevention and treatment are currently the focus of most research. Dose verification is an important step for reducing the improper dose deposition during radiotherapy. To mend the traditional gel dosimeters for 3D dose verification, a novel rare-earth nanoparticle-based composite gel was prepared, which has good radioluminescence property and reusability. It is a promising phantom material for the new 3D gel dosimeter. TEM, DLS, FT-IR, TGA, and spectrofluorometer were used to determine the chemical structure, micromorphology, and optical performance. Compared to the traditional gel dosimeters, the composite gel has a good linear relationship between the light intensity excited by X-ray and the tube current. Furthermore, it may measure the dose distribution immediately in situ , which reduces errors and saves time. This work provides a new idea for the research of 3D gel dosimeters and promotes the safe and effective use of radiotherapy.

研究领域: 医学物理 · 放射治疗 · 材料科学
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CHEMOSPHERE · 2023 · IF 8.8

New insight into PAH4 induced hepatotoxicity and the dose-response assessment in rats model

Miao Yang,Yuxuan Lu,Weifeng Mao,Liping Hao

PAH4 (sum of benzo[a]pyrene, chrysene, benz[a]anthracene and benzo[b]fluoranthene) has been proposed as better marker than benzo[a]pyrene to assess total PAHs exposure in foodstuffs. However, the toxicological behaviors of PAH4 combined exposure remain unclear. This study aimed to investigate PAH4 toxicity effects with non-targeted metabolomics approach and evaluate the external and internal dose-response relationships based on benchmark dose (BMD) analysis. Male Sprague-Dawley rats were treated by gavage with vehicle (corn oil) or four doses of PAH4 (10, 50, 250, 1000 μg/kg·bw) for consecutive 30 days. After the final dose, the liver, blood and urine samples of rats were subsequently collected for testing. The concentrations of urinary mono-hydroxylated PAHs metabolites (OH-PAHs) including 3-hydroxybenzo[a]pyrene (3-OHB[a]P), 3-hydroxychrysene (3-OHCHR) and 3-hydroxybenz[a]anthracene (3-OHB[a]A) were determined to reflect internal PAH4 exposure. Our results showed PAH4 exposure increased relative liver weight and serum aspartate aminotransferase (AST) activity and caused hepatocyte swelling and degeneration, implying hepatotoxicity induced by PAH4. Serum metabolomics suggested PAH4 exposure perturbed lipid metabolism through upregulating the expression of glycerolipids metabolites, which was evidenced by markedly increased serum triglyceride (TG) level and hepatic TG content. Additionally, urinary OH-PAHs concentrations presented strong positive correlations with the external dose, indicating they were able to reflect PAH4 exposure. Furthermore, PAH4 exposure led to a dose-response increase of hepatic TG content, based on which the 95% lower confidence value of BMDs for external and internal doses were estimated as 5.45 μg/kg·bw and 0.11 μmol/mol·Cr, respectively. In conclusion, this study suggested PAH4 exposure could induce hepatotoxicity and lipid metabolism disorder, evaluating the involved dose-response relationships and providing a basis for the risk assessment of PAHs.

研究领域: 毒理学 · 环境健康 · 代谢组学
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MEDICAL PHYSICS · 2023 ·Vol. 50 ·期 10 ·6624-6636 · IF 3.8

Development of a quasi-3D dosimeter using radiochromic plastic for patient-specific quality assurance

Jin Dong Cho,Hyeongmin Jin,Seongmoon Jung,Jaeman Son,Chang Heon Choi,Jong Min Park,Jin Sung Kim,Jung-in Kim

Background Patient-specific QA verification ensures patient safety and treatment by verifying radiation delivery and dose calculations in treatment plans for errors. However, a two-dimensional (2D) dose distribution is insufficient for detecting information on the three-dimensional (3D) dose delivered to the patient. In addition, 3D radiochromic plastic dosimeters (RPDs) such as PRESAGE ® represent the volume effect in which the dosimeters have different sensitivities according to the size of the dosimeters. Therefore, to solve the volume effect, a Quasi-3D dosimetry system was proposed to perform patient-specific QA using predetermined-sized and multiple RPDs. Purpose For patient-specific quality assurance (QA) in radiation treatment, this study aims to assess a quasi-3D dosimetry system using an RPD. Methods Gamma analysis was performed to verify the agreement between the measured and estimated dose distributions of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). We fabricated cylindrical RPDs and a quasi-3D dosimetry phantom. A practicability test for a pancreatic patient utilized a quasi-3D dosimetry device, an in-house RPD, and a quasi-3D phantom. The dose distribution of the VMAT design dictated the placement of nine RPDs. Moreover, a 2D diode array detector was used for 2D gamma analysis (MapCHECK2). The patient-specific QA was performed for IMRT, VMAT, and stereotactic ablative radiotherapy (SABR) in 20 prostate and head-and-neck patients. For each patient, six RPDs were positioned according to the dose distribution. VMAT SABR and IMRT/VMAT plans employed a 2%/2 mm gamma criterion, whereas IMRT/VMAT plans used a 3%/2 mm gamma criterion, a 10% threshold value, and a 90% passing rate tolerance. 3D gamma analysis was conducted using the 3D Slicer software. Results The average gamma passing rates with 2%/2 mm and 3%/3 mm criteria for relative dose distribution were 91.6% ± 1.4% and 99.4% ± 0.7% for the 3D gamma analysis using the quasi-3D dosimetry system, respectively, and 97.5% and 99.3% for 2D gamma analysis using MapCHECK2, respectively. The 3D gamma analysis for patient-specific QA of 20 patients showed passing rates of over 90% with 2%/2 mm, 3%/2 mm, and 3%/3 mm criteria. Conclusions The quasi-3D dosimetry system was evaluated by performing patient-specific QAs with RPDs and quasi-3D phantom. The gamma indices for all RPDs showed more than 90% for 2%/2 mm, 3%/2 mm, and 3%/3 mm criteria. We verified the feasibility of a quasi-3D dosimetry system by performing the conventional patient-specific QA with the quasi-3D dosimeters.

CAS / MDL: 129-73-7 558-13-4
研究领域: 医学物理 · 放射肿瘤学
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Heliyon · 2022 · IF 3.776

Accurate in vivo real-time determination of the hydrogen concentration in different tissues of mice after hydrogen inhalation

Wenjun Zhu,Qianqian Gu,Boyan Liu,Yanhong Si,Huirong Sun,Jingjie Zhong,Yi Lu,Dan Wang,Junli Xue,Shucun Qin

As an antioxidant, anti-inflammatory and anti-apoptotic agent, hydrogen (H 2 ) shows a promising potential in basic and clinical research against various diseases owing to its safety and efficacy. However, knowledge involving its underlying mechanisms of action, dosage effects, and dose duration remains limited. Previously, the dynamics of H 2 concentrations in different tissues of rats after exogenous H 2 inhalation had been detected by our team. Here, sequential changes of H 2 concentrations in different tissues of another most commonly used experimental rodent mice were monitored in real time with an electrochemical H 2 gas sensor during continuous different concentrations of H 2 inhalation targeting on five tissues including brain, liver, spleen, kidney, and gastrocnemius. The results showed that the H 2 saturation concentrations varied among tissues significantly regardless of the concentration of H 2 inhaled, and they were detected the highest in the kidney but the lowest in the gastrocnemius. Meantime, it required a significant longer time to saturate in the thigh muscle. By comparing the H 2 saturation concentrations of mice and rats, we found that there were no differences detected in most tissues except the kidney and spleen. Both gas diffusion and bloodstream transport could help the H 2 reach to most organs. The results provide data reference for dosage selection, dose duration determination to ensure optimal therapeutic effects of H 2 for mice experiments.

研究领域: 医学 · 生物化学
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Analytical Methods · 2023 · IF 3.1

A rhodamine coumarin-derived fluorescence probe that selectively detects Fe3+ and measures radiation doses

Danni Qin,Yaqi Han,Hao Jiang,Liang Hu

We synthesized a fluorescence ratiometric probe by combining coumarin and rhodamine B with ethylenediamine to sense Fe3+ and measure ionizing radiation doses. The presence of Fe3+ caused rhodamine to transition from a closed helical structure to an open-ring structure. Additionally, fluorescence resonance energy transfer (FRET) occurred between coumarin and rhodamine B. As a result, the fluorescence intensity at 405 nm (I405) due to coumarin was decreased, whereas that at 585 nm (I585) derived from open-ring structure rhodamine B was increased. The ratio of I585 and I405 (I585/I405) linearly increased as the Fe3+ concentration increased. The probe sensed Fe3+ in a 0–110 μM range, with a lower limit of detection (LOD) of 0.226 μM. Inspired by Fricke dosimeters, we extended the probe to measure X-ray doses using the fluorescence methodology. The probe measured X-ray doses in a 0–30 Gy range with a lower LOD of 0.5 Gy. Additionally, the dosing capability was independent of the dosing rates. Our probe showed potential for detecting Fe3+ and measuring ionizing radiation doses.

研究领域: 分析化学 · 放射生物学
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JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY · 2022 · IF 6.814

All-in-one device for mapping the interactive effects of photodynamic therapy dosimetry in tumor gaseous microenvironment

Shu Zhang,Yuewu Li,Rui Dong,Weitao Li,Zhiyu Qian,Yamin Yang

Photodynamic therapy (PDT) elicits cell death , vascular damage , or/and anti-tumor host immune response upon activating the administered photosensitive drug by an appropriate light source. Because PDT is heavily dependent on tissue oxygen (O 2 ) in essence, the concentration-dependent impact of O 2 on tailoring cellular response to PDT remains an in-depth investigation. As a multifaceted modality, optimal combinations of photosensitizer (PS) concentration, light dose, and O 2 delivery are critical to achieve ideal therapeutic outcomes. We herein present a fully integrated all-in-one device for the in vitro assessment of PDT efficacy synchronizing the quantitative control of three PDT disciplines simultaneously, aiming at 1) identifying the influence of varying gaseous microenvironments on PDT; and 2) determining the contribution of each PDT factor and estimating the strength of their synergic effect. The gas-gradient-generating unit for contactless headspace O 2 delivery and spatial light control filtering layer in our device could either work as a stand-alone module or combine to screen a range of experimental PDT parameters. By sweeping a total of 128 conditions over four 5-aminolevulinic acid (5-ALA) concentrations, four light dosages, and eight O 2 levels in one single experiment, we determined the main effects of the three key PDT agents and highlighted the interactive effect between 5-ALA and light after full-factorial statistical analysis. Our device is not only a versatile tool for predicting PDT efficacy during the translational study but also provides valuable multidimensional information for the interrelation between key PDT factors, which may expedite clinical PDT dosimetry and furnish new insights for the fundamental understanding of photobiological processes.

CAS / MDL: 5451-09-2
研究领域: 生物医学工程 · 癌症研究 · 治疗模式 · 生物物理学 · 药物递送系统
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