PET and NIR optical imaging using self-illuminating Cu-doped chelator-free gold nanoclusters

Self-illuminating fluorescence imaging without autofluorescence background interference has recently aroused more research interests in molecular imaging. Currently, only a few self-illuminating probes were developed, based mainly on toxic quantum dots such as CdSe, CdTe. Herein, we report a novel design of nontoxic self-illuminating gold nanocluster (⁶⁴Cu-doped AuNCs) for dual-modality positron emission tomography (PET) and near-infrared (NIR) fluorescence imaging based on Cerenkov resonance energy transfer (CRET). PET radionuclide ⁶⁴Cu was introduced by a chelator-free doping method, which played dual roles as the energy donor and the PET imaging source. Meanwhile, AuNCs acted as the energy acceptor for NIR fluorescence imaging. ⁶⁴Cu-doped AuNCs exhibited efficient CRET-NIR and PET imaging both in vitro and in vivo. In a U87MG glioblastoma xenograft model, ⁶⁴Cu-doped AuNCs showed high tumor uptake (14.9 %ID/g at 18 h) and produced satisfactory tumor self-illuminating NIR images in the absence of external excitation. This self-illuminating nanocluster with non-toxicity and good biocompatibility can be employed as a novel imaging contrast agent for biomedical applications, especially for molecular imaging.     

Cancer stem cell therapy using doxorubicin conjugated to gold nanoparticles via hydrazone bonds

Nanoparticle-mediated delivery of chemotherapies has demonstrated enhanced anti-cancer efficacy, mainly through the mechanisms of both passive and active targeting. Herein, we report other than these well-elucidated mechanisms, rationally designed nanoparticles can efficiently deliver drugs to cancer stem cells (CSCs), which in turn contributes significantly to the improved anti-cancer efficacy. We demonstrate that doxorubicin-tethered gold nanoparticles via a poly(ethylene glycol) spacer and an acid-labile hydrazone bond mediate potent doxorubicin delivery to breast CSCs, which reduces their mammosphere formation capacity and their cancer initiation activity, eliciting marked enhancement in tumor growth inhibition in murine models. The drug delivery mediated by the nanoparticles also markedly attenuates tumor growth during off-therapy stage by reducing breast CSCs in tumors, while the therapy with doxorubicin alone conversely evokes an enrichment of breast CSCs. Our findings suggest that with well-designed drug delivery system, the conventional chemotherapeutic agents are promising for cancer stem cell therapy.     

Rose-bengal-conjugated gold nanorods for in vivo photodynamic and photothermal oral cancer therapies

Gold nanorods (GNRs) conjugated with rose bengal (RB) molecules exhibit efficient singlet oxygen generation when illuminated by 532 nm green light and high photothermal efficiency under 810 nm near-infrared (NIR) irradiation. In vitro experiments show that reactive oxygen species generated by green light and hyperthermia produced by NIR light constitute two different mechanisms for cancer cell death. The RB-GNRs also exhibit improved photodynamic efficacy by enhancing the uptake of RB by cancer cells. In vivo experiments are conducted on hamster cheek pouches to resemble the human oral cancer conditions more accurately to assess the therapeutic effectiveness. Compared to the single photodynamic therapy (PDT) or photothermal therapy (PTT), the RB-GNRs with combined PDT-PTT capabilities provide better therapeutic effects against oral cancer and have large potential in cancer treatment.     

Secondary Antibody Response Elicited in vitro with Chicken γ Globulin

The plaque-forming cell (PFC) response of spleen cells from mice primed 30-90 days previously with chicken y globulin (CGG) plus adjuvant was studied after restimulation in vitro with 1 pg to 100 μg CGG per culture. The peak response (100 to 500 PFC per 10⁶ cells), elicited with 0.1 μg CGG, was detected five days after restimulation. The 100 μg level of CGG suppressed the PFC response to CGG, but did not decrease the primary PFC response to sheep red blood cells (SRBC) of other, control cultures. Plaques detected with CGG coupled immunologically to SRBC were clearer but not more numerous than those detected with CGG coupled chemically to SRBC. The system described permits the investigation of cellular mechanisms involved in the antibody response to a soluble protein antigen and is, therefore, ideally suited to elucidation of factors which enhance or suppress antibody biosynthesis and immunologic memory.     

The World Health Organization reference reagent for vascular endothelial growth factor,VEGF165

Preparations of human sequence recombinant vascular endothelial growth factor-165 (VEGF₁₆₅) synthesized in Escherichia coli were formulated and lyophilized at NIBSC. Following evaluation at NIBSC, the first preparation, 01/424, has been distributed since 2002 as a NIBSC research reagent, but shows variation between ampoules in the volume and crystalline appearance of the lyophilized plug. A second preparation, 02/286, was subsequently lyophilized in a different formulation. Preparation 02/286 has now been evaluated in a collaborative study for its suitability to serve as a reference standard, and compared with preparation 01/424, by five laboratories using in vitro bioassays or immunoassays. On the basis of the results reported here, the World Health Organization (WHO) established the preparation coded 02/286 as the WHO reference reagent (RR) for human VEGF₁₆₅, with an assigned unitage of 13,000 units per ampoule. Details on ordering the WHO RR can be found at www.nibsc.ac.uk.     

Synthesis of a 14C‐labeled FPTase inhibitor via a Pd‐catalyzed cyanation with Zn(14CN)2 and via bromo[14C]acetic acid

¹⁴C‐Labeled farnesyl‐protein transferase inhibitor 1a was required for drug metabolism studies. The first approach was to synthesize ¹⁴C‐labeled 1b using Zn(¹⁴CN)₂ in a Pd‐catalyzed cyanation. A second approach was to prepare labeled 1c with the ¹⁴C‐label in the piperazine ring. All metabolites from 1b were non‐radioactive whereas the same metabolites from 1c were all radioactive and quantifiable. Copyright © 2008 John Wiley & Sons, Ltd.     

A new chemical method of synthesis of modified nucleoside [32P]phosphates

A simple method of chemical phosphorylation for modified nucleosides with [³²P]orthophosphoric acid in the presence of BrCN is described. The yields of 5′‐[³²P]nucleoside monophosphates achieved are 50–65% at nominal specific radioactivities of ca. 1000 Ci/mmol. The mechanism of phosphorylation in the presence of heterocyclic amines is studied. Copyright © 2008 John Wiley & Sons, Ltd.     

从一次盲点调查结果中分析体外诊断产品的临床使用情况和改进建议

就一次临床化验盲点调查的结果．看不同检测项目在不同等级医院中的出错频率．讨论体外诊断产品在临床中应如何使用．给出临床实验室开展体外诊断项目的监管建议。     

纸层析-分光光度法测定发酵液中L-异亮氨酸

鉴于在菌种选育工作中必须准确测定菌株产酸水平,要求有可行的测定方法,对简单易行的纸层析 分光光度法测定发酵液中L 异亮氨酸质量进行了系统的研究,研究发现:选用合适的显色剂、层析溶剂及洗脱剂的同时选择最佳吸收波长、最佳洗脱时间及适宜的点样量,可以提高该测定方法的准确度和精密度,从而在菌种筛选过程中准确地测定发酵液中L 异亮氨酸质量.     

99mTc标记葡萄糖99mTc-EC-DG在正常小鼠体内的分布研究

目的研究^99mTc标记葡萄糖99mTc-EC-DG在正常小鼠体内的生物学分布规律,用于临床肿瘤显像作基础研究.方法正常昆明小鼠48只,分8组,每组6只,实验前小鼠禁食8 h以上.尾静脉注射^99mTc-EC-DG 3.7 MBq (100 μCi) 后5 min、15 min、30 min、1 h、2 h、4 h、8 h和24 h放血处死,取心、肝、脾、肺、脑、肾、肌肉、骨、小肠、胃和血液等组织或器官,称重并测量其放射性,计算每克组织百分注射剂量率(%ID/g).结果^ 99mTc-EC-DG主要经肾脏代谢,脑不吸收^99mTc-EC-DG,肌肉组织摄取亦较少.各组织、器官的百分剂量率在1 h内除血液下降稍慢外,其余均有明显下降.结论^ 99mTc-EC-DG标记方便,体内外稳定性好,小鼠体内生物学分布表明其可能是一种较好的葡萄糖代谢显像剂.