MAGNETIC NANOPARTICLE ENGINEERING via MICROREACTION TECHNOLOGY

无机纳米颗粒（NPs）具有极大地改变现有材料以及设计广泛的变革性新产品的潜力。它们具有散装材料中所没有的独特的磁性、光学、电子和催化特性，因此它们为解决医疗保健、能源、运输、气候和安全领域一些最紧迫的全球挑战提供了机会。纳米粒子为检测和治疗许多疾病提供了理想的解决方案。作为靶向给药系统，它们可以改善市场上已有药物的性能。它们有助于开发新的治疗策略，如抗癌药物输送、延长产品生命周期和降低医疗成本。磁性纳米颗粒（MNPs）具有令人兴奋的潜在生物医学应用。它们已被考虑用于诊断，如磁共振成像、磁颗粒成像和用于传感的磁免疫分析，以及治疗，如热疗癌症治疗（使用靶向磁加热杀死癌细胞）。癌症是全球疾病的主要原因，2008年估计有1270万新发癌症病例。如果主要癌症的近期趋势继续下去，到2030年，癌症负担将增加到每年2220万新病例。癌症也是全世界死亡的主要原因，2008年有760万人死亡（约占所有死亡人数的13%）。目前市场上的磁性氧化铁NPs的饱和磁化强度较低，因此需要较高的浓度和较高的外磁场才能实现有效加热。该提案旨在制造更高磁矩的纳米粒子，与目前使用的磁性纳米粒子（MNPs）相比，具有更高的性能。所提出的过渡元素MNPs是非常理想的，但是在精确控制尺寸和尺寸分布的情况下合成它们是出了名的困难。此外，它们容易氧化，这有不利的影响，因为它们的磁性（磁矩）显着降低或完全失去。用惰性材料（如二氧化硅和金）涂覆纯金属和合金MNPs已成为保护核心MNPs免受氧化的明显方法。由于涂层不完全，这已被证明是具有挑战性的，并导致NPs的长期化学不稳定性。此外，目前大多数MNP合成都是成批进行的，重复性差。在这个项目中，我们将使用一种新颖的方法对MNPs进行“桥”涂层。我们将进一步采用连续流技术，这是一个更好地控制MNPs合成的有利工具。它可以精确控制操作条件，以及成核，生长和涂层步骤的空间分离。我们拥有一支由工程师、化学家和物理学家组成的多学科团队，他们将结合他们在流动微反应器技术、材料化学和物理方面的强大专业知识，通过设计新的合成路线和利用连续流动处理提供的增强功能，推动材料设计和发现的前沿。我们将通过在体外测试MNPs杀死癌细胞的功效，证明我们的合成方法在磁性热疗方面的成功，磁性热疗是抗癌临床应用中最受追捧的应用之一。

Inorganic nanoparticles (NPs) have the potential to dramatically modify existing materials as well as engineer a broad range of transformative new products. They have unique magnetic, optical, electronic, catalytic properties not encountered in bulk materials and as such they present the opportunity to address some of the most pressing global challenges in healthcare, energy, transport, climate and security. Nanoparticles offer ideal solutions for detecting and treating many diseases. Used as targeted drug-delivery systems, they can improve the performance of medicines already on the market. They enable the development of new therapeutic strategies such as anti-cancer drug delivery, extending product life cycles and reducing healthcare costs. Magnetic nanoparticles (MNPs) have exciting potential biomedical applications. They have been considered for diagnostics, such as magnetic resonance imagining, magnetic particle imaging and magnetic immunoassay for sensing, as well as in therapeutics, such as hyperthermia cancer treatment (using targeted magnetic heating to kill cancer cells). Cancer is a leading cause of disease worldwide with an estimated 12.7 million new cancer cases occurring in 2008. If recent trends in major cancers continue, the burden of cancer will increase to 22.2 million new cases each year by 2030. Cancer is also a leading cause of death worldwide, with 7.6 million deaths (around 13% of all deaths) in 2008. Magnetic iron oxide NPs currently available in the market have low saturation magnetisation, and therefore require high concentration as well as high external magnetic field to achieve effective heating. This proposal aims to fabricate higher magnetic moment NPs, with enhanced performance as compared to currently used magnetic nanoparticles (MNPs). The proposed transition elements MNPs are highly desirable, but it has been notoriously difficult to synthesise them with accurate control of size and size distribution. Moreover, they are prone to oxidation which has detrimental effects, as their magnetic properties (magnetic moment) are significantly reduced or entirely lost. Coating pure metal and alloy MNPs with inert materials such as silica and gold has been the obvious approach to protect the core MNPs from oxidation. This has proved challenging due to incomplete coating, and leads to long term chemical instability of NPs. Furthermore, most of MNP synthesis is currently done in batch, which suffers from poor reproducibility. In this project, we will use a novel approach for "bridge" coating of MNPs. We will further employ continuous flow technology which is an enabling tool for better control of the synthesis of MNPs. It allows accurate control of operating conditions, as well as spatial separation of the nucleation, growth and coating steps. We have a multidisciplinary team of engineers, chemists and physicists who will combine their strong expertise in flow microreactor technology, materials chemistry and physics to push the frontiers in materials design and discovery by engineering novel synthetic routes and by taking advantage of the enhanced functionalities offered by continuous flow processing. We will demonstrate the success of our synthetic approach in magnetic hyperthermia, one of the most sought after clinical applications in combating cancer, by testing the MNPs efficacy for killing cancer cells in vitro.