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biodistribution and Toxicity Assessment of Superparamagnetic Iron Oxide Nanoparticles In Vitro and In Vivo

Current Medical Science 2018年第6期38卷 1096-1102页

作者： Qin YU Xiao-qin XIONG Lei ZHAO Ting-ting XU Hao BI Rong FU Qian-hua WANG Department of Clinical Laboratory Wuhan Blood CenterWuhan 430000China School of Chemistry and Life Science Hubei University of EducationWuhan 430205China Department of Obstetrics and Gynecology Union HospitalHuazhong University of Science and TechnologyWuhan 430022China

biodistribution and toxicity assessment are critical for safe clinical use of newly developed *** iron oxide nanoparticles (SPION)are effective carriers for targeted drug *** study aimed to examine the toxicity and biodistribution of SPION coated with polyethylenimine (PEI)(SPION-PEI)designed for small interfering RNA (siRNA) delivery both in vitro and in ***-PEI/siRNA complexes were prepared at different weight *** effects of SPION-PEI/siRNA on HSC-T6 cell viability were determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT).Rats were divided into three groups:a control group,a normal-saline group and a SPION-PEI/siRNA *** a single intravenous injection,in vivo nanoparticle biodistribution and accumulation were evaluated by Prussian blue staining in the heart,liver,spleen,lung and kidney 8 h,24 h,and 7 days after the *** distribution was histologically studied at the three time points by measuring ironpositive areas (μm2)in organ sections stained with Prussian *** same organs were analyzed by H&E staining for any possible histopathological ***,biochemical indexes such as alanine amino transaminase (ALT),aspartate transaminase (AST),blood urea nitrogen (BUN)and creatinine (CREA)were also assessed at all experimental time *** exhibited that the SPION-PEI could retard siRNA altogether at weight ratios above *** assay showed that SPION-PEI loaded with siRNA had low *** vivo study revealed that the liver and spleen were the major sites of SPION-PEI/siRNA *** iron content was significantly increased in the liver and spleen,peaking 24 h after intravenous injection and then declining *** evidence was found of irreversible histopathological damage to any of the organs *** results suggested that most SPION-PEI/siRNA complexes were distributed in the liver and spleen,which might be the targ

关键词： superparamagnetic iron oxide nanoparticles toxicity biodistribution Prussian blue staining

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Effect of glutathione on in vivo biodistribution and clearance of surface-modified small Pd nanosheets

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Science China Chemistry 2015年第11期58卷 1753-1758页

作者： Yizhuan Huang Xiaolan Chen Saige Shi Mei Chen Shaoheng Tang Shiguang Mo Jingping Wei Nanfeng Zheng State Key Laboratory for Physical Chemistry of Solid Surfaces Department of Chemistry College of Chemistry and Chemical EngineeringXiamen University

Plasmonic Pd nanosheets have been emerging as promising materials for application in near-infrared(NIR) photothermal therapy(PTT) of cancer. However, animal in mice studies indicated that the original synthesized poly(vinylpyrrolidone)(PVP)-protected small Pd nanosheets(Pd-PVP) and some further surface-modified small Pd nanosheets such as Pd-PEG(SH) easily accumulated in reticuloendothelial system(RES) organs(liver, spleen, etc.) and were difficult to be cleared from these organs quickly. In the work, we surprisingly found that glutathione(GSH) could promote the clearance of surface-modified small Pd nanosheets(e.g. Pd-PVP, Pd-PEG(SH) and Pd-GSH) from the RES organs efficiently. The effects of GSH on the biodistribution and clearance of different surface-modified Pd nanosheets were investigated. Our results indicated that these surface-modified Pd nanosheets with or without GSH added caused no morbidity at target primary organs, and GSH can promote the clearance of different surface-modified Pd nanosheets in the order of Pd-PVP≈Pd-PEG(SH)>Pd-GSH. This study suggests that glutathione could be an attractive reagent for promoting nanomaterials eliminated from the reticuloendothelial systems(RES).

关键词： noble metal nanomaterials glutathione biodistribution renal clearance

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Preparation of a New Radiolabeled Biomaterial and Its biodistribution in Mice

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Journal of Bionic Engineering 2013年第4期10卷 514-521页

作者： Jinshu Ma Zhenning Liu Fang Wang Qinghai Zhou Chao Feng Fan Li Department of Pathogenobiology Norman Bethune College of Medicine Jilin University Changchun 130021 P. R. China Key Laboratory of Bionic Engineering (Ministry of Education) Jilin University Changchun 130022 P. R. China State Key Laboratory of Polymer Physics and Chemistry Changchun Institute of Applied Chemistry Changchun 130022 P. R. China Department of Neurology First Hospital Jilin University Changchun 130021 P. R. China

Biomaterials have attracted more attention from biomedical research in recent years. Yet there are still unmet demands for current biomaterials, such as the reduction of local inflammation of the implantation site. Poly-Propylene Carbonate （PPC）, a polymer with ester bonds on COz backbone, degrades to CO2 and water, which are natural components of human body, yielding less inflammatory response than traditional biomaterials. However, the tensile strength and heat resistance properties of PPC are less ideal. In order to improve the properties of PPC, we have developed a new PPC （M-PPC）, modified by mixing with Poly-3-Hydroxybutyrate （PHB）. Here, we report the biodistribution profiles of PPC and M-PPC, their biocompatibility and toxicity. 125I-radiolabeled PPC and M-PPC were prepared and their biodistribution in Balb/c mice were investigated. Then acute systemic toxicity and haemolysis assays were conducted to study their toxicity and biocompatibility respectively. Results show that M-PPC has a good potential to be used as bone repair materials because it possesses typical biodistribution pattern in major organs, minimal toxicity and good biocompatibility.

关键词： biomaterial poly-propylene carbonate PPC biodistribution

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Pharmacokinetics and biodistribution of polymeric micelles of paclitaxel with Pluronic P123

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Acta Pharmacologica Sinica 2006年第6期27卷 747-753页

作者： Li-mei HAN Jie GUO Li-jun ZHANG Qing-song WANG Xiao-ling FANG~2 Department of Pharmaceutics.School of Pharmacy,Fudan University,Shanghai 200032,China Department of Pharmaceutics School of Pharmacy Fudan University Shanghai China

Aim:To investigate the preparation,in vitro release,in vivo pharmacokineticsand tissue distribution of a novel polymeric micellar formulation of paclitaxel(PTX)with Pluronic ***:The polymeric micelles of paclitaxel with PluronicP123 were prepared by a solid dispersion *** characteristics of micellesincluding particle size distribution,morphology and in vitro release of PTX frommicelles were carried ***-loaded micellar solutions were administered throughthe tail vein to healthy Sprague-Dawley rats and Kunming strain mice to assessthe pharmacokinetics and tissue distribution of PTX,***,thecommercially available intravenous formulation of PTX,was also administered ***:By using a dynamic light scattering sizer and a transmissionelectron microscopy,it was shown that the PTX-loaded micelles had a mean sizeof approximately 25 nm with narrow size distribution and a spherical *** continuously released from Pluronic P 123 micelles in release medium contain-ing 1 mol/L sodium salicylate for 24 h at 37℃.In the pharmacokinetic assessment,t1/2βand AUC of micelle formulation were 2.3 and 2.9-fold higher than that of *** the PTX-loaded micelles increased the uptake of PTX in the plasma,ovary and uterus,lung,and kidney,but decreased uptake in the liver and brain inthe biodistribution ***:Polymeric micelles using Pluronic P123can effectively solubilize PTX,prolong blood circulation time and modify thebiodistribution of PTX.

关键词： paclitaxel micelle Pluronic P123 pharmacokinetics biodistribution

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A Novel Technique for the Preparation of ^(125)I-5-trimethylstannyl-1-(2-deoxy-2-fluoro-beta-D-arabino-furanosyl) Urail and Its biodistribution Pattern in Kunming Mice

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2011年第5期31卷 693-695页

作者：胡佳张永学孙逊李多兰李崇佼覃春霞曹卫兰晓莉 Department of Nuclear Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology Hubei Province Key Lab of Molecular Imaging

In this study, a novel technique for the preparation of 125I-5-trimethylstannyl-1-（2-deoxy-2-fluoro-beta-D-arabinofuranosyl） urail （FIAU） was developed, 125I-FIAU biodistribution profile was detected in Kunming mice and the possibility of using FTAU radio-labeling for reporter gene imaging was explored. 5-trimethylstannyl-1-（2-deoxy-2-fluoro-beta-D-arabinofuranosyl） urail （FTAU） was labeled with radioiodine （125I）. A rotary evaporation method was used to remove excess methanol. The reactant was purified through a Sep-Pak C18 reversal phase column. The radiochemical purity and in vivo stability were determined using silica gel thin layer chromatography （TLC）. The biodistribution of 125I-FIAU in Kunming mice was also detected. The results showed that 125I-FIAU could be radiolabeled effectively with FTAU, with mean labeling rate being （81±0.38）% （n =5）. The mean radiochemical purity of （98.01±0.40）% （n=5） was achieved after a reversal phase Sep-park column purification. 125I-FIAU was stable when incubated in normal human serum or in saline at 37°C, with a radiochemical purity 〉96% during a 0.5-24 h time period. Biological experiments exhibited rapid clearance of 125I-FIAU from the blood pool. 125I-FIAU was mostly excreted by kidneys. 125I-FIAU in myocardium dropped conspicuously after 8 h and there was hardly retention at 24 h. We were led to concluded that the new method of radioiodinization of FTAU for the preparation of 125I-FIAU is easy, highly effective and stable in vivo. The biodistribution of 125I-FIAU in Kunming mice showed it can serve as an imaging probe for myocardial reporter genes.

关键词： reporter gene FTAU radioiodine labeling biodistribution

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Preliminary radioimmunoimaging and biodistribution of ^131iodine-labeled single-chain antibody fragment against progastrin-releasing peptide（31-98） in small cell lung cancer xenografts

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Chinese Medical Journal 2014年第11期127卷 2007-2011页

作者： Hong Zhihui Shi Yizhen Liu Zengli Zhou Xiaolin Yang Yi Tang Jun Department of Nuclear Medicine the Second Affiliated Hospital of Soochow University Suzhou Jiangsu 215004 China Department of Radiology and Nuclear Medicine China Institute for Radiation Protection Taiyuan Shanxi 030006 China

Background Monoclonal antibodies （mAbs） such as DD3,raised against progastrin-releasing peptide（31-98）（ProGRP（31-98）） antigen,have been used to target small cell lung cancer （SCLC）.However,as an intact mAb,DD3 is cleared slowly from the body,with an optimal radioimmunoimaging time of 72 *** recently,a singlechain antibody fragment has demonstrated reduced excretion time in blood and normal tissues and is increasingly used in diagnostic cancer ***,it potentially increases the radioimmunoimaging ***,there have been few studies with this antibody *** aim of this study was to characterize the preliminary radioimmunoimaging and biodistribution of 1311I-anti-ProGRP（31-98）scFv in nude mice bearing SCLC *** Anti-ProGRP（31-98） scFv was used to detect ProGRP expression by flow cytometry analysis and immunohistochemistry.131I-anti-ProGRP（31-98） scFv was injected intravenously into healthy Kunming mice and the percentage injected dose per gram （%ID/g） in various organs was ***,the %ID/g and tumor/non-tumor ratio in xenograft-bearing mice was *** injection of 131I-anti-ProGRP（31-98） scFv,treated mice were imaged at 1,24,and 30 *** the tumor/base ratios were *** ProGRP was highly expressed in NCI-H446 cells and xenograft *** metabolism of 131I-anti-ProGRP（31-98） scFv in healthy mice was consistent with a first-order and two-compartment model; T1/2α and T1/2β were 10.2 minutes and 5 hours 18 minutes,*** %ID/g of 131I-anti-ProGRP（31-98） scFv in xenografts was much higher than in healthy tissues at 12 hours after injection,reaching a maximum of （5.38±0.92） %ID/g at 24 *** imaging of xenograft tissue was achieved as early as 1 hour post-injection and persisted until 30 hours,with 24 hours proving *** 131I-anti-ProGRP（31-98）scFv shows highly selective tumor uptake with low accumulation in normal tissues and rapid blood clearance,

关键词： 131I-anti-ProGRP(31-98)scFv ProGRP(31-98) small cell lung cancer biodistribution radioimmunoimaging

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Radiolabeling LyP-1 peptide and preliminary biodistribution evaluation in mice bearing MDA-MB-435 xenografts

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Chinese Medical Journal 2013年第3期126卷 471-475页

作者： YU Ming-ming WANG Rong-fu CHEN Yue-hua ZHOU Hai-zhong DENG Xiao-hu Department of Nuclear Medicine Clinical Medical College of Yangzhou University Yangzhou Jiangsu 225001 China Department of Nuclear Medicine Peking University First Hospital Beijing 100034 China

Background Recent studies have shown the LyP-1 peptide can home to either tumor lymphatics or the tumor cells and be internalized by targeted cells. This study aimed to investigate the possibility of using Na1311 labeled LyP-1 peptide as an imaging agent or a therapeutic radiopharmaceutical in breast carcinoma and its metastasis. Methods The 10-mer cyclic peptide contained the LyP-1 sequence （YCGNKRTRGC） was synthesized by the solid phase method. Disulfide bonds between the cysteines maintain the cyclic structure. The LyP-1 peptide was labeled with Na1311 using the chloramine-T method. The [1311] LyP-1 peptide and a [1311] control peptide were injected via tail vein into nude mice bearing MDA-MB-435 tumor xenografts. biodistribution and imaging results in vivo were obtained. Results The labeling efficiencies of LyP-1 peptide reached 80%＋5% （n=5）. The radiochemical purity was about 96%. The radiochemical purity of the labeled compound remains 92% at 24 hours in human serum at 37~C. In the biodistribution studies, the [1311] LyP-1 peptide accumulated in the tumor to a higher level than in other organs. The [1311] LyP-1 peptide can successfully image the tumor in nude mice bearing MDA-MB-435 tumor xenografts. Conclusions The LyP-1 peptide could be effectively labeled with Na1311 and the labeled compound is stable in human serum at 37℃ for 24 hours. The high specificity of [1311] LyP-1 peptide suggests it may be a promising new radiotracer for identifying tumors.

关键词： LyP-1 peptide MDA-MB-435 xenografts biodistribution imaging

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Antitumor activity and biodistribution of DHA-NLC formulation in sarcoma 180-bearing mice

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Journal of Chinese Pharmaceutical Sciences 2013年第4期22卷 348-354页

作者：张晓云乔华赵鹏倪京满史彦斌兰州大学药学院甘肃兰州730000 兰州大学第一医院药剂科甘肃兰州730000 兰州大学第一医院肿瘤科甘肃兰州730000

Lipid nanoparticles have become attractive for its prominent properties recent years. In this paper, in vivo anti-tumor efficacy of nanostructured lipid carrier of dihydroartemisinin （DHA-NLC） were evaluated in sarcoma 180-bearing mice model through intraperitoneal （i.p.） administration. In vivo biodistribution was also investigated in Kunming mice bearing S180. Results demonstrated that the intraperitoneally injected DHA-NLC could significantly inhibit tumor growth at the dose levels of 20, 40 and 80 mg/kg, and their inhibition rates were 71.24%, 79.20% and 85.74%, respectively. The biodistribution of DHA after intraperitoneal injection of DHA-NLC in S180-bearing mice is remarkably different from the DHA solution. Therefore, DHA encapsulated in NLC does demonstrate superior anticancer effect to DHA suspension on S 180-bearing mice at the same dose and displayed a dose-dependent antitumor efficacy.

关键词： Nanostructured lipid carrier Antitumor Sarcoma 180 biodistribution

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Development of novel interferon alpha2b muteins and study the pharmacokinetic and biodistribution profiles in animal model

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Journal of Biomedical Science and Engineering 2012年第3期5卷 104-112页

作者： Ratih Asmana Ningrum Desi Eria Rahmatika Debbie Sofie Retnoningrum Aang Hanafiah Wangsaatmadja Yeyet Cahyati Sumirtapura Heni Rachmawati Labeled Compound and Radiometry Division National Nuclear Energy Agency Bandung Indonesia School of Pharmacy Bandung Institute of Technology Bandung Indonesia

Novel human interferon alpha 2b (hIFNα2b) muteins were developed by substituting cysteine residue (C) at positions 2 and 99 with aspartic acid residues (D). The mutein forms were then studied for pharmacokinetic profile. In addition, the influence of charge on the protein structure was tested in vivo for the biodistribution pattern. Codon substitutions were performed by Polymerase Chain Reaction (PCR)-based site-directed mutagenesis on a previously constructed synthetic hIFNα2b open reading frame (ORF) cloned in pET32b expression plasmid. The result of nucleotide sequencing analysis confirmed that all codons were replaced successfully without any additional mutation. Three mutant forms of hIFNα2b ORF were overexpressed in Escherichia coli BL21 (DE3) resulted in three muteins: hIFNα2b C2D, hIFNα2b C99D, hIFNα2b C2D C99D. To follow the kinetic and localization of the mutein interferon after intravenous administration, Tc99m was used to label the proteins. In particular of elimination half-life, it was shown that hIFNα2b C2D C99D > hIFNα2bC2D > hIFNα2bC99D > wild type. hIFNα2b C2D C99D mutein showed highest blood accumulation after 30 minutes administration. Taken together, the charge of hIFNα2b seems to be responsible for the fate of hIFNα2b in vivo.

关键词： Mutein Human Interferon Alpha2b Amino Acid Substitution PCR Based Site Directed Mutagenesis Tc99mlabeling Pharmacokinetic biodistribution Protein Charge

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The biodistribution and kinetics of the Samarium-153 labeled avidin,streptavidin and biotin

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Journal of Medical Colleges of PLA(China) 2001年第3期16卷 179-182页

作者：李贵平朱承谟江旭锋冯国伟张圣国 Department of Nuclear Medicine Nanfang Hospital First Military medical University Guangzhou 510515China Department of Nuclear Medicine Ruijin Hospital Shanghai Second Medical University Shanghai 200025China

Objective:To labelavidin(Av)or streptavidin(SA)with 153 Sm by takingadvantageof thehighbindingaffin-ityof biotinto Av or ***:A biotinderivative(DTPA-biotin)wasradiolabelledwith 153 Sm andthenboundto Av or *** vivo kineticsandbiodistributionof 153 Sm-labeledAv,SA ***:153 Sm-Avwascharacterizedby rapidclearancefromthebloodwithhighliverandrenaluptake;153 Sm-SAwas clearedfromthebloodslowlywithhighretentionintheliver,spleenandkidney,whereas 153 Sm-DTPA-biotinmetabolismwas accelerated,*** sion:Thebiodistributiondifferenceof SAandAvmay providean experimentalbasisfor theselectionof differentcomponentsof avidin-biotinsystemin pretagetingradioim-munoimagingandradioimmunotherapy.

关键词： avidin-biotin system 153Sm labeling biodistribution

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