Bio-functional Magnetic Nanoparticles: Novel High-Efficiency Targeting Agents for Localised Treatment of Metastatic Cancers

生物功能磁性纳米颗粒：用于转移性癌症局部治疗的新型高效靶向剂

• 批准号: EP/G062072/1
• 负责人: Quentin Pankhurst
• 金额: $ 205.16万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FG062072%2F1
• 关键词: Bio; functional; Magnetic; Nanoparticles; Novel

One of the greatest healthcare challenges facing the world today is the treatment of metastatic cancer. Although we know a great deal about how to treat tumours once they grow more than a few millimetres in size, it is the unseen me-tastases that spread out from a primary site that more often than not are the cause of fatalities. We are forced to resort to systemic treatments, to chemotherapy and radiotherapy, which place the entire physiology under severe strain, af-fecting healthy cells almost as much as they do the cancer cells. There is a pressing need for viable alternatives, and clinicians and scientists have been pursuing such goals for decades. Although there have been successes, for the most part it has been impossible to deliver therapeutic agents to the sites of metastases in sufficiently high doses. Attention has turned to 'payload' methods, where the targeting biomolecule is used to carry a therapeutic agent to the cancer, and some external stimulus is applied to activate it. The best of these are based on the use of inorganic nanoparticles which, under stimulation, are designed to release heat. These hyperthermia approaches are ideally suited to cancers, which are highly susceptible to heat-induced cellular stress. Hyperthermia also has great potential as an adjuvant therapy, since just a degree or two of local heating can significantly increase the effectiveness of chemotherapy and radiotherapy, reducing their required doses and thereby reducing the harmful side-effects. Even so, to date there has been little real success in attempts to implement localised hyperthermia, despite promising bench results. The key failure lies in the required dose-response characteristics of the therapy, which exceed the capa-bilities of the best approaches attempted so far. One approach, volumetric induction heating of magnetic nanoparticles using megahertz applied fields, is intrinsically efficient. However, even here efforts are hampered by a reliance on 30-year-old induction heating electronics - more befitting an arc-welding workshop than a hospital clinic - so that only one clinical trial has yet been attempted. It is therefore no wonder that our announcement earlier this year of a new breakthrough invention - an induction heat-ing circuit we call the Magnetic Alternating Current Hyperthermia (MACH) system - was greeted with enormous media attention. The MACH system embodies three ground-breaking innovations which together enable, for the first time, construction of an extremely high performance, robust system that can feasibly be used in the clinic. Of particular note, it allows for a hand-held coil to be attached to the heater, and for miniaturisation or even catheterisation of the appli-cator. The prospects are suddenly wide open for real clinical application of hyperthermia to treat metastatic cancer, and for widespread exploitation of this UK-owned technology in an exceptionally large market. To translate this promise into achievement requires significant efforts, and most importantly, well-focused efforts. To this end we have consulted widely and brought together an excellent team of academics, clinicians and companies, from start-ups to conglomerates, to work together on an implementation plan. Key to this plan is to move as fast as possible to clinical outcomes, to engage quickly with patients, clinicians and health services to establish efficacy and credibility, and to build a platform for innovation for years to come. We have chosen to adopt a dual approach of (1) proving the clinical efficacy of the MACH system for localised hyperthermia on two especially well suited cancer exemplars - head and neck cancer and lung cancer; and (2) developing 'stealth' antibody-tagged magnetic nanoparticles suitable for intravenous injection, and able to evade the reticulo-endothelial system and accumulate at metastatic sites. These then are the goals of our Nanotechnology Grand Challenge.

当今世界面临的最大医疗挑战之一是转移性癌症的治疗。尽管我们知道如何治疗肿瘤，一旦它们长出几毫米大小，但从原发部位扩散出来的看不见的我的味道往往是致命的原因。我们被迫求助于全身治疗、化疗和放射治疗，这使整个生理系统处于严重的压力之下，对健康细胞的影响几乎与对癌细胞的影响一样大。目前迫切需要可行的替代品，临床医生和科学家几十年来一直在追求这样的目标。尽管已经取得了成功，但在大多数情况下，以足够高的剂量将治疗剂输送到转移部位是不可能的。人们的注意力转向了“有效载荷”方法，在这种方法中，靶向生物分子被用来携带一种治疗药物到癌症，并施加一些外部刺激来激活它。其中最好的是基于无机纳米颗粒的使用，在刺激下，这些纳米颗粒被设计成释放热量。这些热疗方法非常适合癌症，因为癌症非常容易受到热诱导的细胞压力的影响。热疗作为一种辅助治疗也有很大的潜力，因为只需一两度的局部加热就可以显著提高化疗和放射治疗的有效性，减少它们所需的剂量，从而减少有害的副作用。即便如此，到目前为止，实施局部热疗的尝试几乎没有取得真正的成功，尽管试验室的结果很有希望。关键的失败在于治疗所需的剂量-反应特性，这超出了迄今尝试的最佳方法的能力。一种方法，使用兆赫外加磁场对磁性纳米颗粒进行体积感应加热，本质上是有效的。然而，即使是在这里，由于对已有30年历史的感应加热电子设备的依赖，这些努力也受到了阻碍--比起医院诊所，它更适合弧焊车间--以至于只尝试了一次临床试验。因此，难怪我们今年早些时候宣布的一项新的突破性发明--一种我们称为磁交流热疗(MACH)系统的感应加热电路--受到了媒体的极大关注。马赫系统包含三项突破性的创新，这三项创新首次共同构建了一个可以在临床上可行地使用的极高性能、健壮的系统。特别值得注意的是，它允许将手持线圈连接到加热器上，并使应用程序小型化甚至导尿化。突然之间，热疗治疗转移性癌症的真正临床应用的前景变得广阔起来，这项英国拥有的技术在一个异常巨大的市场上得到了广泛的开发。要将这一承诺转化为成就，需要付出巨大的努力，最重要的是，需要有针对性的努力。为此，我们进行了广泛的咨询，并召集了一支由学者、临床医生和公司组成的优秀团队，从初创企业到企业集团，共同制定实施计划。这一计划的关键是尽快取得临床成果，迅速与患者、临床医生和卫生服务机构接触，以建立疗效和可信度，并在未来几年建立一个创新平台。我们选择采用双重方法：(1)证明MACH系统对头颈癌和肺癌这两个特别合适的癌症样本进行局部热疗的临床疗效；(2)开发适合静脉注射的“隐形”抗体标记的磁性纳米颗粒，并能够避开网状内皮系统并在转移部位聚集。这些就是我们纳米技术大挑战的目标。

项目成果

Incorporation of paramagnetic, fluorescent and PET/SPECT contrast agents into liposomes for multimodal imaging.

• DOI: 10.1016/j.biomaterials.2012.09.070
• 发表时间: 2013-01
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Mitchell N;Kalber TL;Cooper MS;Sunassee K;Chalker SL;Shaw KP;Ordidge KL;Badar A;Janes SM;Blower PJ;Lythgoe MF;Hailes HC;Tabor AB
• 通讯作者: Tabor AB

Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles.

• DOI: 10.2147/ijn.s94255
• 发表时间: 2016
• 期刊: International journal of nanomedicine
• 影响因子: 8
• 作者: Kalber TL;Ordidge KL;Southern P;Loebinger MR;Kyrtatos PG;Pankhurst QA;Lythgoe MF;Janes SM
• 通讯作者: Janes SM

Nanoscience: v. 1: Nanostructures Through Chemistry

纳米科学：v. 1：通过化学研究纳米结构

• 发表时间: 2012
• 作者: O'Brien, Paul;Green, Mark;Pattrick, Richard;Corr, Serena;Imai, Hiroaki;Haigh, Sarah;Young, Robert;Pradeep, T.
• 通讯作者: Pradeep, T.