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Preparation and Characterization of Folate Targeting Magnetic Nanomedicine Loaded with Cisplatin
Minqiang Xie,Yiming Xu,Jie Liu,Tao Zhang,Hongzheng Zhang
Journal of Nanomaterials , 2012, DOI: 10.1155/2012/921034
Abstract: We used Aldehyde sodium alginate (ASA) as modifier to improve surfactivity and stability of magnetic nanoparticles, and folate acid (FA) as targeting molecule. Fe3O4 nanoparticles were prepared by chemical coprecipitation method. FA was activated and coupled with diaminopolyethylene glycol (NH2-PEG-NH2). ASA was combined with Fe3O4 nanoparticles, and FA-PEG was connected with ASA by Schiff’s base formation. Then Cl- in cisplatin was replaced by hydroxyl group in ASA, and FA- and ASA-modified cisplatin-loaded magnetic nanomedicine (CDDP-FA-ASA-MNPs) was prepared. This nanomedicine was characterized by transmission electron microscopy, dynamic lighterring scattering, phase analysis light scattering and vibrating sample magnetometer. The uptake of magnetic nanomedicine by nasopharyngeal and laryngeal carcinoma cells with folate receptor positive or negative expression were observed by Prussian blue iron stain and transmission electron microscopy. We found that CDDP-FA-ASA-MNPs have good water-solubility and stability. Mean diameter of Fe3O4 core was 8.17 ±0.24 nm, hydrodynamic diameters was 110.90±1.70 nm, and zeta potential was ?26.45±1.26 mV. Maximum saturation magnetization was 22.20 emu/g. CDDP encapsulation efficiency was 49.05±1.58% (mg/mg), and drug loading property was 14.31±0.49% (mg/mg). In vitro, CDDP-FA-ASA-MNPs were selectively taken up by HNE-1 cells and Hep-2 cells, which express folate receptor positively.
188re标记叶酸偶联白蛋白纳米微球对skov3人卵巢癌生长抑制作用研究  [PDF]
唐秋莎,陈道桢,臧嘉,郭彩琴
天津医药 , 2013,
Abstract: ??【】?目的??观察核素标记叶酸靶向白蛋白纳米微球(188re-folate-cddp/hasmnp)对skov3人卵巢癌细胞生长作用的影响。?方法?建立人卵巢癌细胞skov3裸鼠模型,并将64只荷瘤鼠随机分成8组,每组8只,分别为(a)阴性对照组;(b)采用cddp方案化疗的单纯化疗组;(c)核素靶向内照射的单纯放疗组;(d)磁感应热疗的单纯热疗组;(e)化疗联合放疗组;(f)化疗联合热疗治疗组;(g)放疗联合热疗治疗组;(h)热疗、化疗、放疗联合治疗组。各组经治疗后,观察肿瘤生长增殖情况,计算肿瘤质量抑制率,观察肿瘤组织病理变化。??结果??各治疗组的肿瘤质量均低于对照组(p<0.05),且与其他治疗组相比,热疗、化疗、放疗联合治疗组的肿瘤质量最低(p<0.05)。??结论??磁感应热疗、化疗、核素靶向内照射放疗的联合作用能有效抑制卵巢癌的生长,对卵巢癌治疗具有潜在应用前景。
188Re radiopharmaceuticals for radiosynovectomy: evaluation and comparison of tin colloid, hydroxyapatite and tin-ferric hydroxide macroaggregates
Eduardo Savio, María Ures, Patricia Zeledón, Victoria Trindade, Andrea Paolino, Virginia Mockford, Antonio Malanga, Marcelo Fernández, Javier Gaudiano
BMC Medical Physics , 2004, DOI: 10.1186/1471-2385-4-1
Abstract: Three radiopharmaceutical formulations, tin colloid, hydroxyapatite particles (HA) and ferric hydroxide macroaggregates coated with tin colloid (FHMA), were physically characterized (number, volume and surface of the particles). For this purpose laser diffraction methodology was used. To evaluate cavity leakage of activity the following studies in New Zealand rabbits were performed: scintigraphic images for 48 hr after intraarticular injection of each radiopharmaceutical, biodistribution at 48 hr and urine samples collection during the first 24 hr post-radiopharmaceutical administration.Labeling procedures for 188Re-HA and 188Re-Sn-FHMA were labour intensive while 188Re-Sn was easily prepared. Furthermore, 188Re-Sn colloid offered the greatest surface area in the 2–10 microm range and was obtained with a radiochemical purity over 95%, while percentage of bound activity for 188Re-HA and 188Re-Sn-FHMA were 55% and 92% respectively. Stability was verified for the three radiopharmaceuticals for 24 hr. Scintigraphic studies and biodistribution in rabbits after intraarticular administration of the radiopharmaceuticals showed relevant activity only in the knee, this being over 90% of the residual activity in the whole body at 48 hr in every case. Renal elimination of 188Re-Sn colloid and 188Re-Sn-FHMA was detected by activity measurements in urine samples, during the first 12 hr post-radiopharmaceutical injection.The percentage of activity retained in the knee was 69.1% for 188Re-Sn colloid, 55.1% for 188Re-Sn-FHMA and 33.6% for 188Re-HA.The 188Re-Sn colloid was easy to prepare, minimum facilities were required, was stable for 24 hr and showed minimal leakage from the joint after intraarticular injection into the rabbit's knee. Furthermore, 188Re-Sn colloid has greater retention in the knee when it is compared with the other radiopharmaceuticals, so it could provide the best therapeutic effect/absorbed dose ratio for the patient.Three principal diseases associated with syn
Theranostic Studies of Human Sodium Iodide Symporter Imaging and Therapy Using 188Re: A Human Glioma Study in Mice  [PDF]
Rui Guo, M. Zhang, Yun Xi, Yufei Ma, Sheng Liang, Shuo Shi, Ying Miao, Biao Li
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0102011
Abstract: Objective To investigate the role of 188Re in human sodium iodide symporter (hNIS) theranostic gene-mediated human glioma imaging and therapy in model mice. Methods The human glioma cell line U87 was transfected with recombinant lentivirus encoding the hNIS gene under the control of cytomegalovirus promoter (U87-hNIS). The uptake and efflux of 188Re were determined after incubating the cells with 188Re. 188Re uptake experiments in the presence of various concentrations of sodium perchlorate were carried out. In vitro cell killing tests with 188Re were performed. U87-hNIS mediated 188Re distribution, imaging and therapy in nude mice were also tested. Results U87-hNIS cell line was successfully established. The uptake of 188Re in U87-hNIS cells increased up to 26-fold compared to control cells, but was released rapidly with a half-life of approximately 4 minutes. Sodium perchlorate reduced hNIS-mediated 188Re uptake to levels of control cell lines. U87-hNIS cells were selectively killed following exposure to 188Re, with a survival of 21.4%, while control cells had a survival of 92.1%. Unlike in vitro studies, U87-hNIS tumor showed a markedly increased 188Re retention even 48 hours after 188Re injection. In the therapy study, there was a significant difference in tumor size between U87-hNIS mice (317±67 mm3) and control mice (861±153 mm3) treated with 188Re for 4 weeks (P<0.01). Conclusion The results indicate that inserting the hNIS gene into U87 cells is sufficient to induce specific 188Re uptake, which has a cell killing effect both in vitro and in vivo. Moreover, our study, based on the function of hNIS as a theranostic gene allowing noninvasive imaging of hNIS expression by 188Re scintigraphy, provides detailed characterization of in vivo vector biodistribution and level, localization, essential prerequisites for precise planning and monitoring of clinical gene therapy that aims to individualize gene therapy concept.
Biodistribution and pharmacokinetics of 188Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice  [cached]
Tsai CC,Chang CH,Chen LC,Chang YJ
International Journal of Nanomedicine , 2011,
Abstract: Chia-Che Tsai1, Chih-Hsien Chang1, Liang-Cheng Chen1, Ya-Jen Chang1, Keng-Li Lan2, Yu-Hsien Wu1, Chin-Wei Hsu1, I-Hsiang Liu1, Chung-Li Ho1, Wan-Chi Lee1, Hsiao-Chiang Ni1, Tsui-Jung Chang1, Gann Ting3, Te-Wei Lee11Institute of Nuclear Energy Research, Taoyuan, 2Cancer Center, Taipei Veterans General Hospital, Taipei, 3National Health Research Institutes, Taipei, Taiwan, ROCBackground: Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR) effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT) image, dosimetry, and therapeutic efficacy of 188Re-labeled nanoliposomes (188Re-liposomes) in a C26 colonic peritoneal carcinomatosis mouse model were evaluated.Methods: Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered 188Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of 188Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with 188Re-liposomes and 5-fluorouracil (5-FU), respectively, were evaluated and compared.Results: In biodistribution, the highest uptake of 188Re-liposomes in tumor tissues (7.91% ± 2.02% of the injected dose per gram of tissue [%ID/g]) and a high tumor to muscle ratio (25.8 ± 6.1) were observed at 24 hours after intravenous administration. The pharmacokinetics of 188Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h). Micro-SPECT/CT imaging of 188Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with images from autoradiography and biodistribution data. Dosimetry study revealed that the 188Re-liposomes did not cause high absorbed doses in normal tissue but did in small tumors. Radiotherapeutics with 188Re-liposomes provided better survival time (increased by 34.6% of life span; P < 0.05), tumor and ascites inhibition (decreased by 63.4% and 83.3% at 7 days after treatment; P < 0.05) in mice compared with chemotherapeutics of 5-fluorouracil (5-FU).Conclusion: The use of 188Re-liposomes for passively targeted tumor therapy had greater therapeutic effect than the currently clinically applied chemotherapeutics dr
Biodistribution and pharmacokinetics of 188Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice
Tsai CC, Chang CH, Chen LC, Chang YJ, Lan KL, Wu YH, Hsu CW, Liu IH, Ho CL, Lee WC, Ni HC, Chang TJ, Ting G, Lee TW
International Journal of Nanomedicine , 2011, DOI: http://dx.doi.org/10.2147/IJN.S23834
Abstract: iodistribution and pharmacokinetics of 188Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice Original Research (4330) Total Article Views Authors: Tsai CC, Chang CH, Chen LC, Chang YJ, Lan KL, Wu YH, Hsu CW, Liu IH, Ho CL, Lee WC, Ni HC, Chang TJ, Ting G, Lee TW Published Date October 2011 Volume 2011:6 Pages 2607 - 2619 DOI: http://dx.doi.org/10.2147/IJN.S23834 Chia-Che Tsai1, Chih-Hsien Chang1, Liang-Cheng Chen1, Ya-Jen Chang1, Keng-Li Lan2, Yu-Hsien Wu1, Chin-Wei Hsu1, I-Hsiang Liu1, Chung-Li Ho1, Wan-Chi Lee1, Hsiao-Chiang Ni1, Tsui-Jung Chang1, Gann Ting3, Te-Wei Lee1 1Institute of Nuclear Energy Research, Taoyuan, 2Cancer Center, Taipei Veterans General Hospital, Taipei, 3National Health Research Institutes, Taipei, Taiwan, ROC Background: Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR) effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT) image, dosimetry, and therapeutic efficacy of 188Re-labeled nanoliposomes (188Re-liposomes) in a C26 colonic peritoneal carcinomatosis mouse model were evaluated. Methods: Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered 188Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of 188Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with 188Re-liposomes and 5-fluorouracil (5-FU), respectively, were evaluated and compared. Results: In biodistribution, the highest uptake of 188Re-liposomes in tumor tissues (7.91% ± 2.02% of the injected dose per gram of tissue [%ID/g]) and a high tumor to muscle ratio (25.8 ± 6.1) were observed at 24 hours after intravenous administration. The pharmacokinetics of 188Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h). Micro-SPECT/CT imaging of 188Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with images from autoradiography and biodistribution data. Dosimetry study revealed that the 188Re-liposomes did not cause high absorbed doses in normal tissue but did in small tumors. Radiotherapeutics with 188Re-liposomes provided better survival time (increased by 34.6% of life span; P < 0.05), tumor and ascites inhibition (decreased by 63.4% and 83.3% at 7 days after treatment; P < 0.05) in mice compared with chemotherapeutics of 5-fluorouracil (5-FU). Conclusion: The use of 188Re-liposomes for passively targeted tumor therapy had greater therapeutic effect than the currently
MNPs@ZIFs催化剂的研究进展  [PDF]
薛松林,晏青,杜艳,姜红,陈日志
化工进展 , 2015, DOI: 10.16085/j.issn.1000-6613.2015.09.015
Abstract: 概括了将金属纳米颗粒(MNPs)嵌入或装载到沸石咪唑酯骨架材料(ZIFs)上构筑MNPs@ZIFs催化剂的方法,包括化学气相沉积法、固体研磨法、溶液浸渍法和自组装法,对其优缺点进行了讨论,并重点介绍了自组装法在制备MNPs@ZIFs催化剂时MNPs空间分布的可调控性;介绍了MNPs@ZIFs催化剂微结构的表征手段,特别是分析MNPs在ZIFs中空间分布的方法;探讨了MNPs@ZIFs催化剂在耦合、氧化、还原等反应中的催化性能,分析了其择形催化功能。在此基础上,提出了今后MNPs@ZIFs催化剂研究的主要方向是制备新型高稳定性且具有大孔径的ZIF材料、精确控制MNPs在ZIFs中的空间分布以及开发MNPs@ZIFs催化剂的工业化制备方法。
Association of ABCC2 and CDDP-Resistance in Two Sublines Resistant to CDDP Derived from a Human Nasopharyngeal Carcinoma Cell Line  [PDF]
Si Ming Xie,Wei Yi Fang,Teng Fei Liu,Kai Tai Yao,Xue Yun Zhong
Journal of Oncology , 2010, DOI: 10.1155/2010/915046
Abstract: Cisplatin (CDDP) is one of the most active drugs to treat nasopharyngeal carcinoma (NPC) patients. To further understand the mechanisms of CDDP-resistance in NPC, two CDDP-resistant sublines (CNE2-CDDP and CNE2-CDDP-5Fu) derived from parental NPC cell line CNE2 were established. It was found that at the IC50 level, the resistance of CNE2-CDDP and CNE2-CDDP-5Fu against CDDP was 2.63-fold and 5.35-fold stronger than that of parental CNE2, respectively. Of the four ABC transporters (ABCB1, ABCC1, ABCC2 and ABCG2) related to MDR, only ABCC2 was found to be elevated both in CDDP-resistant sublines, with ABCC2 located in nucleus of CNE2-CDDP-5Fu but not in CNE2-CDDP and parental CNE2. Further research showed that compared to untreated CNE2, the intracellular levels of CDDP were decreased by 2.03-fold in CNE2-CDDP and 2.78-fold in CNE2-CDDP-5Fu. After treatment with PSC833, a modulator of MDR associated transporters including ABCC2, the intracellular level of CDDP was increased in CDDP-resistant sublines, and the resistance to CDDP was partially reversed from 2.63-fold to 1.62-fold in CNE2-CDDP and from 5.35-fold to 4.62-fold in CNE2-CDDP-5Fu. These data indicate that ABCC2 may play an important role in NPC resistant to CDDP. 1. Introduction Nasopharyngeal carcinoma (NPC) is a major malignant disease of the head and neck region and is endemic to Southeast Asia and Mediterranean basin, especially in Southern China [1, 2]. Since NPC originates from a hidden anatomical site and is more closely associated with advanced clinical stage, the results of conventional radiotherapy technique are unsatisfactory although it is a radiosensitive tumor. Therefore, chemotherapy treatment is a necessary ancillary method for these NPC patients [3, 4]. cis-Diamminedichloroplatinum (CDDP), also known as cisplatin, which is the most active and most frequently employed drugs, is often used to treat distant metastasis or advanced locoregional recurrence of NPC patients, and the chemotherapeutic regimen of CDDP plus 5-fluorouracil (5-Fu) is the main drug combination used in clinical trials [5, 6]. However, inherent and acquired resistance to the drug limits its applications in NPC chemotherapy. The mechanisms of resistance to CDDP are complicated. Of all these mechanisms, the one that is most commonly encountered in the laboratory is the increased efflux of abroad class of hydrophobic cytotoxic drugs that is mediated by one of a family of energy-dependent transporters, known as adenosine triphosphate binding cassette (ABC) transporters [7]. The ABC transporters have the capability to
Human Folate Bioavailability  [PDF]
Veronica E. Ohrvik,Cornelia M. Witthoft
Nutrients , 2011, DOI: 10.3390/nu3040475
Abstract: The vitamin folate is recognized as beneficial health-wise in the prevention of neural tube defects, anemia, cardiovascular diseases, poor cognitive performance, and some forms of cancer. However, suboptimal dietary folate intake has been reported in a number of countries. Several national health authorities have therefore introduced mandatory food fortification with synthetic folic acid, which is considered a convenient fortificant, being cost-efficient in production, more stable than natural food folate, and superior in terms of bioavailability and bioefficacy. Other countries have decided against fortification due to the ambiguous role of synthetic folic acid regarding promotion of subclinical cancers and other adverse health effects. This paper reviews recent studies on folate bioavailability after intervention with folate from food. Our conclusions were that limited folate bioavailability data are available for vegetables, fruits, cereal products, and fortified foods, and that it is difficult to evaluate the bioavailability of food folate or whether intervention with food folate improves folate status. We recommend revising the classical approach of using folic acid as a reference dose for estimating the plasma kinetics and relative bioavailability of food folate.
Magnetoelectric MnPS3 thiophosphate as a new candidate for ferrotoroidicity  [PDF]
Eric Ressouche,Mickael Loire,Virginie Simonet,Rafik Ballou,Anne Stunault,Andrew Wildes
Physics , 2010, DOI: 10.1103/PhysRevB.82.100408
Abstract: We have revisited the magnetic structure of manganese phosphorus trisulfide MnPS3 using neutron diffrac- tion and polarimetry. MnPS3 undergoes a transition toward a collinear antiferromagnetic order at 78 K. The resulting magnetic point-group breaks both the time reversal and the space inversion thus allowing a linear magnetoelectric coupling. Neutron polarimetry was subsequently used to prove that this coupling provides a way to manipulate the antiferromagnetic domains simply by cooling the sample under crossed magnetic and electrical fields, in agreement with the nondiagonal form of the magnetoelectric tensor. In addition, this tensor has, in principle, an antisymmetric part that results in a toroidic moment and provides with a pure ferrotoroidic compound.
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