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体内肿瘤的靶向检测与治疗
nanomicrolett 2019-4-28 12:46
本文亮点 1 以量子点为核、介孔SiO 2 空心球为壳,制备中空核-壳结构纳米体系。 2 结合PET和光学成像的优点,用双模态PET/光学成像进行癌症的协同诊断。 3 成功实现了肿瘤血管的靶向治疗,增加了药物在肿瘤部位的停留时间和靶向特异性。 内容简介 PET(Positron emission tomography, 正电子发射断层扫描) 是核医学领域最先进的临床检查影像技术,高分辨率的优点使其能够广泛应用于肿瘤和心肺疾病等临床诊断。而 双模态或多模态分子探针技术 在诊断或治疗中可获得更全面的信息。在生物医学领域, 介孔硅材料 具有大比表面积、大孔容和多样孔道结构等特性,在药物运输方面具有良好的应用前景。而实现药物运输的关键是介孔硅能将不同类型的药物分子有效封装在介孔硅孔道内部,从而使治疗药物免于酶解。 美国威斯康星大学Weibo Cai团队 设计了一种用于肿瘤血管靶向和双模态PET/光学成像的 中空核-壳结构的 SiO 2 纳米体系 : 64 Cu-NOTA-QD@HMSN-PEG-TRC 105 。该体系具有良好的靶向特异性和出色的成像能力,使得诊断结果更加可靠。此工作将脉管系统靶向、pH敏感药物递送、双模态成像三者结合到单个平台中,将中空核-壳结构SiO 2 纳米体系应用于图像引导的肿瘤靶向药物递送,有效增强了癌症的诊断和治疗。 图文导读 1 QD@HMSN 的 合成 QD@HMSN SiO 2 中空核-壳纳米结构的合成和功能化示意图。 2 体内血管靶向和PET成像 从PET图像和ROI分析中获得的定量数据显示,与非靶向组和阻断组相比,靶向组中的肿瘤摄取显著增强。 3 药物装载和光学成像 在中空核-壳纳米结构的QD@HMSN NPs中,药物装载量显著增加至1266 mg/g(DOX重量/NP重量)。增加的药物负荷可能有利于增强癌症化疗的疗效,同时由于每次治疗需要的纳米颗粒剂量较小,从而降低了纳米载体的体内细胞毒性。 作者简介 主要研究方向: 1)多模态分子成像剂的开发; 2)癌症的分子疗法; 3)纳米技术及其生物医学应用。 课题组主页: http://mi.wisc.edu/index.htm 原文链接: https://link.springer.com/article/10.1007/s40820-018-0216-2 相关阅读 1 综述:碳纳米管和石墨烯的生物传感应用 2 综述 : 碳纳米管内嵌Cu/Ag纳米颗粒复合物的植物化学功能化及高抗菌抗癌特性 3 牛血清白蛋白耦联磁性Fe3O4 纳米颗粒提高生物相容性与磁热疗性能 4 金纳米颗粒单层和多层细胞模型在纳-微界面上相互作用的尺寸依赖性 5 双模式成像和pH/近红外响应药物输送:新型金纳米棒@聚丙烯酸/磷酸钙核壳纳米结构 关于我们 Nano-Micro Letters是上海交通大学主办的英文学术期刊,主要报道纳米/微米尺度相关的最新高水平科研成果与评论文章及快讯,在Springer开放获取(open-access)出版。可免费获取全文,欢迎关注和投稿。 E-mail: editorial_office@nmletters.org Tel: 86-21-34207624
3624 次阅读|0 个评论
[转载]一次血液检测筛查八种类型癌症
zhpd55 2018-1-25 01:57
一次血液检测筛查八种类型癌症 --该方法为多种最常见癌症的早期发现提供了独特的新框架 Credit: Elizabeth Cook and Kaitlin Lindsay 约翰•霍普金斯大学Kimmel 癌症研究中心( Johns Hopkins Kimmel Cancer Center )的研究人员开发了一种能够筛选八种常见类型癌症的单一血液检测,该方法还有助于癌症的定位。 这种名为CancerSEEK的检测方法是一项独特的无创多分析测试,它可同时评估八种癌症蛋白的水平和血液中循环DNA的癌症基因突变。这项检测旨在筛选占美国癌症死亡人数60%以上的八种常见类型的癌症。其中可以由该方法进行筛查的五种癌症,此前不具备任何筛查检测方法。 该文资深作者,肿瘤与病理学教授 Nickolas Papadopoulos, Ph.D., 表示:“将选定的不同生物标记物联合用于早期检测有可能改变我们筛查癌症的方式,该检测是基于与药物组合治疗癌症相同的原理。” 该研究的发现在线发表在《科学杂志》 Science 上。 该文第一作者,约翰•霍普金斯大学医学院的M.D.-Ph.D.学生Joshua Cohen说:“循环肿瘤DNA突变可能是癌症的高度特异性标记物。为了利用这种内在的特异性,我们试图开发一个小而强大的特异性标记物组合来检测绝大多数癌症的至少一个突变。而事实上,使该组合规模尽量的小,这对于减少假阳性结果至关重要,并且还能让人负担得起筛查检测费用。” 研究人员探索了数百个基因和40个蛋白质标记物,并最终将其数量减少到16个基因和8个蛋白。 他们指出,这种分子检测旨在仅进行癌症筛查,因此它与其它分子检测方法有所不同,后者是旨在通过分析大量癌症相关基因来发现癌症治疗的靶点。 在这个研究中,该测试对癌症的特异性大于99%。肿瘤学教授兼路德维希中心(the Ludwig Center)的联合主任 Kenneth Kinzler, Ph.D. 表示:“非常高的特异性是必不可少的,因为假阳性结果会使患者接受不必要的有创随访检查和手术以确认癌症的存在。在被用于812名健康对照时,该检测仅产生了7个假阳性结果。 该检测在1,005名非转移性I至III期卵巢癌,肝癌,胃癌,胰腺癌,食管癌,结直肠癌,肺癌或乳腺癌患者中进行了评估。 该检测的总体敏感度中位数(即发现癌症的能力)为70%,其范围从卵巢癌的98%至乳腺癌的33%。对于目前不具备筛查检测的五种癌症(卵巢癌,肝癌,胃癌,胰腺癌和食管癌)而言,其敏感度在69%至98%之间。 开发了该检测的算法的肿瘤和生物统计副教授 Cristian Tomasetti, Ph.D .表示:“我们的分类方法的一个新颖之处在于,它将观察DNA突变以及几种蛋白质表达水平的可能性结合起来,以得出最终的检测结果。该方法的另一个新颖之处在于它使用了机器学习来使检测能够在83%的患者中把肿瘤准确定位到很少的几个解剖部位。” 虽然目前的检测还不能检测出每一种癌症,但是它能够检测到很多以前很可能不会被发现的癌症。路德维希中心(the Ludwig Center)的联合主任,Clayton肿瘤学教授兼霍华德•休斯医学研究所(Howard Hughes Medical Institute)研究员 Bert Vogelstein, M.D. ,表示:“在大多数最具希望的癌症治疗方法中,很多是仅能使少数癌症患者获益。如果我们要在早期癌症检测方面取得进展,我们必须以更现实的方式进行研究,要认识到没有任何一种方法可以检测到所有的癌症。” 为了确定CancerSEEK检测应该包括的分析物,研究小组使用了30多年来约翰•霍普金斯大学路德维希中心(Johns Hopkins Ludwig Center)的癌症遗传学研究数据,以及来自许多其它机构的数据:路德维希中心是首个癌症遗传图谱的诞生地。 为了精确地确定在CancerSEEK检测中使用的DNA碱基的最佳数量,研究人员使用了基于收益递减原理的方法来使该检测包括那些对癌症检测确实有用的DNA标记物,并剔除了没有增益效果的DNA标记物,其结果是得到一个相对较小的高选择性DNA标记物组合。 医学,外科和放射学副教授,消化内科临床主任和多学科胰腺囊肿项目主任 Anne Marie Lennon, M.D., Ph.D. 说:“最理想的状态是,癌症能够被尽早地检测出来,并且通过手术就可以治愈;即使是单纯手术无法治愈的癌症,在其疾病发展程度较低时,对治疗的反应也会更好。” Single Blood Test Screens for Eight Cancer Types Provides unique new framework for early detection of the most common cancers Release Date: January 18, 2018 Share Fast Facts @HopkinsKimmel researchers developed a single #cancertest that screens for 8 cancer types and identifies the cancer’s location. - Click to Tweet Credit: Elizabeth Cook and Kaitlin Lindsay Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer. The test, called CancerSEEK, is a unique noninvasive, multianalyte test that simultaneously evaluates levels of eight cancer proteins and the presence of cancer gene mutations from circulating DNA in the blood. The test is aimed at screening for eight common cancer types that account for more than 60 percent of cancer deaths in the U.S. Five of the cancers covered by the test currently have no screening test. “The use of a combination of selected biomarkers for early detection has the potential to change the way we screen for cancer, and it is based on the same rationale for using combinations of drugs to treat cancers,” says Nickolas Papadopoulos, Ph.D., senior author and professor of oncology and pathology. The findings were published online by Science on Jan. 18, 2018. “Circulating tumor DNA mutations can be highly specific markers for cancer. To capitalize on this inherent specificity, we sought to develop a small yet robust panel that could detect at least one mutation in the vast majority of cancers,” says Joshua Cohen, an M.D.-Ph.D. student at the Johns Hopkins University School of Medicine and the paper’s first author. “In fact, keeping the mutation panel small is essential to minimize false-positive results and keep such screening tests affordable.” The investigators initially explored several hundred genes and 40 protein markers, whittling the number down to segments of 16 genes and eight proteins. They point out that this molecular test is solely aimed at cancer screening and, therefore, is different from other molecular tests, which rely on analyzing large numbers of cancer-driving genes to identify therapeutically actionable targets. In this study, the test had greater than 99 percent specificity for cancer. “Very high specificity was essential because false-positive results can subject patients to unnecessary invasive follow-up tests and procedures to confirm the presence of cancer,” says Kenneth Kinzler, Ph.D. , professor of oncology and co-director of the Ludwig Center. The test was used on 812 healthy controls and produced only seven false-positive results. The test was evaluated on 1,005 patients with nonmetastatic, stages I to III cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung or breast. The median overall sensitivity, or the ability to find cancer, was 70 percent and ranged from a high of 98 percent for ovarian cancer to a low of 33 percent for breast cancer. For the five cancers that have no screening tests—ovarian, liver, stomach, pancreatic and esophageal cancers—sensitivity ranged from 69 percent to 98 percent. “A novelty of our classification method is that it combines the probability of observing various DNA mutations together with the levels of several proteins in order to make the final call,” says Cristian Tomasetti, Ph.D ., associate professor of oncology and biostatistics, who developed the algorithm. “Another new aspect of our approach is that it uses machine learning to enable the test to accurately determine the location of a tumor down to a small number of anatomic sites in 83 percent of patients.” Although the current test does not pick up every cancer, it identifies many cancers that would likely otherwise go undetected. “Many of the most promising cancer treatments we have today only benefit a small minority of cancer patients, and we consider them major breakthroughs. If we are going to make progress in early cancer detection, we have to begin looking at it in a more realistic way, recognizing that no test will detect all cancers,” says Bert Vogelstein, M.D., co-director of the Ludwig Center, Clayton Professor of Oncology and Howard Hughes Medical Institute investigator. To zero in on the analytes they included in their CancerSEEK test, the research team pulled data from more than three decades of cancer genetics research generated at their Ludwig Center at Johns Hopkins, where the first genetic blueprints for cancer were created, as well as data from many other institutions. To precisely determine the optimal number of DNA bases to assess in the CancerSEEK test, the researchers used a method based on diminishing returns. “The more DNA bases you assay, the more mutations you are capable of finding, but eventually you reach a point of diminishing returns,” explains Cohen. “We designed our test to reflect this point of diminishing returns, including the DNA markers that were useful to detecting the cancers and eliminating those that did not add benefit.” The result was a relatively small panel of highly selective DNA markers. “This test represents the next step in changing the focus of cancer research from late-stage disease to early disease, which I believe will be critical to reducing cancer deaths in the long term,” says Vogelstein. CancerSEEK is noninvasive and can, in principle, be administered by primary care providers at the time of other routine blood work. “This has the potential to substantially impact patients. Earlier detection provides many ways to improve outcomes for patients. Optimally, cancers would be detected early enough that they could be cured by surgery alone, but even cancers that are not curable by surgery alone will respond better to systemic therapies when there is less advanced disease,” says Anne Marie Lennon, M.D., Ph.D. , associate professor of medicine, surgery and radiology, clinical director of gastroenterology and director of the Multidisciplinary Pancreatic Cyst Program. The investigators feel that a test that will be used routinely for cancer screening must have a cost in line with or less than other currently available screening tests for single cancers, such as colonoscopy. They envision that the CancerSEEK test will eventually cost less than $500. Larger studies of the test are currently under way. In addition to Cohen, Papadopoulos, Lennon, Tomasetti, Kinzler and Vogelstein, other participants include Lu Li, Yuxuan Wang, Christopher Thorburn, Bahman Afsari, Ludmila Danilova, Christopher Douville, Ammar Javed, Fay Wong, Austin Mattox, Ralph Hruban, Christopher Wolfgang, Michael Goggins, Marco Dal Molin, Tian-Li Wang, Richard Roden, Alison Klein, Janine Ptak, Lisa Dobbyn, Joy Schaefer, Natalie Silliman, Maria Popoli, Joshua Vogelstein, James Browne, Robert Schoen, Randall Brand, Jeanne Tie, Peter Gibbs, Hui-Li Wong, Aaron Mansfield, Jin Jen, Samir Hanash, Massimo Falconi, Peter Allen, Shibin Zhou, Chetan Bettegowda and Luis Diaz. The research was supported by the Lustgarten Foundation for Pancreatic Cancer Research, the Virginia and D.K. Ludwig Fund for Cancer Research, The Commonwealth Fund, the John Templeton Foundation, the Clinomics Program, Mayo Clinic Center for Individualized Medicine, the Mayo Clinic Biobank, the Sol Goldman Center for Pancreatic Cancer Research, The Michael Rolfe Pancreatic Cancer Research Foundation, the Benjamin Baker Scholarship, the Gray Foundation, the Early Detection Research Network, Susan Wojcicki and Dennis Troper, the Marcus Foundation, the Conrad N. Hilton Foundation, the Howard Hughes Medical Institute, and National Institutes of Health Grants P50-CA62924, P50-CA102701, CA06973, GM-07309, and U01CA152753. COI: Nickolas Papadopoulos, Shibin Zhou, Kenneth Kinzler, Luis Diaz and Bert Vogelstein are founders of Personal Genome Diagnostics, Inc. and PapGene, Inc. Vogelstein and Kinzler are on the Scientific Advisory Board of Sysmex-Inostics, and Vogelstein is on the Scientific Advisory Board of Exelixis GP. These companies and others have licensed technologies from Johns Hopkins, and Papadopoulos, Kinzler, Diaz and Vogelstein receive equity or royalties from these licenses. The terms of these arrangements are being managed by The Johns Hopkins University in accordance with its conflict of interest policies. More information, including a copy of the paper, can be found online at the Science press package at http://www.eurekalert.org/jrnls/sci . You will need your user ID and password to access this information.
个人分类: 新观察|1768 次阅读|0 个评论
TED新技术:利用手机APP实现癌症的低成本早期诊断
热度 3 zhengchen0 2014-10-28 20:57
今天习惯性地拿TED当新闻看,听到一个 很神奇的技术发明 。 该技术由Jorge Soto发明, 它可以大大提早癌症 诊断,为患者争取更多的治疗时机,并且检测成本只有现在手段的1/50。整个检测过程已经快和验孕棒差不多了。 其主要原理是不同的癌症引起变异的microRNA不同,使得microRNA成为检测癌症最理想的指示因子。 但是microRNA检测的技术难点是其基因链很短,且差异微小。Jorge Soto成功研制出一种简易检测技术,可以通过一个smart phone对 96个 microRNA 耗时约 60分钟的 生化反应 进行 拍照,记录下不同样本变绿的时间和变绿的程度。 将其结果进行数据分析,并将分析结果与已有的医学数据库 比对从而确诊。 尽管他们的研究还在初期,他们已经成功识别出胰腺癌、肺癌、乳腺癌和肝癌的 microRNA变异特征 组 。 最可爱的是,为了让更多的病患早日受益,Jorge Soto将该项发明免费共享,其数据开源可查。 虽然特定RNA指挥特定的蛋白质合成,但RNA到底什么时候合成蛋白质,合成多少却由microRNA指挥 不同的癌症对应不同的microRNA变异组合 可供测试的96样本预制生化反应盒 将检测盒放到一个3D打印的盒子里面进行约60分钟的生化反应,并用智能手机上的应用对其反应过程进行拍照记录 检测结束后,手机应用对结果进行分析处理 和已有的医学数据库进行比对,图上是他们刚成功确诊的一位胰腺癌患者显示的比对结果 ---- 外行人听报告的笔记,欢迎专家解释。
个人分类: TED|5731 次阅读|3 个评论
纳米石墨烯应用于癌症诊断
热度 3 zhpd55 2012-3-7 10:01
纳米石墨烯应用于癌症诊断
据美国《化学与工程新闻》( CEN )周刊 2012 年 2 月 28 日 报道,美国 麦迪逊威斯康辛大学( University of Wisconsin-Madison )的研究人员 , 已经成功将纳米石墨烯应用于活体老鼠肿瘤的诊断和治疗。 碳材料可能会使肿瘤成像或者传递抗癌药物具有很低的毒性的主要材料。 通过同位素标记的石墨烯氧化物,应用于老鼠的肿瘤诊断, 正电子断层扫描仪( positron-emission tomography )得到的 血管周围的肿瘤目标抗体积淀图示中,黄色箭头所指的就是血管周围的肿瘤目标抗体积淀图示。 石墨烯在医学上的应用研究:首例鼠体肿瘤目标石墨烯基成像剂( first graphene-based imaging agent to target a tumor )研究已经获得成功,其研究成果 2012 年 2 月 16 日 已在美国化学会主办的 ACS Nano ( DOI: 10.1021/nn204625e ) 网站公布。这项研究成果有望成为类似于石墨烯探针,能够使抗癌药物直接到达肿瘤病灶甚至直接杀死肿瘤细胞。采用纳米材料来破坏癌细胞令人担忧的问题之一就是材料本身的毒性。所以科学家已经测试了如碳纳米管等材料的毒性以便寻找适宜于携带抗癌分子的低毒性材料。 美国威斯康辛大学医学与公共卫生学院( University of Wisconsin School of Medicine and Public Health )的蔡伟波( Weibo Cai 音译 ) 和他的同事想知道石墨烯是否就是这样一种适宜于医用的低毒性材料 , 他们认为碳薄片具有类似于碳纳米管的结构,因此推测碳薄片的毒性应该类似于碳纳米管。石墨烯具有独特的物理性质 , 从而使它即使没有药物协助也能够杀死肿瘤细胞。 2010 年苏州大学、北京化工大学以及香港城市大学的研究人员合作,对于近红外光线照射石墨烯处理肿瘤,通过光热疗法杀死癌细胞进行过报道( ( Nano Lett. , DOI: 10.1021/nl100996u ). 欲了解更多信息,请浏览原文。 http://doc.sciencenet.cn/DocInfo.aspx?id=8937 http://doc.sciencenet.cn/DocInfo.aspx?id=8935
个人分类: 新科技|6096 次阅读|3 个评论

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