MAGNETIC NANOPARTICLE ENGINEERING via MICROREACTION TECHNOLOGY

无机纳米颗粒(NPs)有可能极大地改变现有材料，并设计出一系列变革性的新产品。它们具有散装材料所没有的独特的磁性、光学、电子、催化性能，因此它们为解决医疗保健、能源、运输、气候和安全方面的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经上市的药物的性能。它们能够开发新的治疗策略，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)在生物医学领域具有广阔的应用前景。它们被考虑用于诊断，如磁共振成像、磁粒子成像和用于传感的磁性免疫分析，以及用于治疗，如热疗癌症治疗(使用靶向磁加热杀死癌细胞)。癌症是世界范围内的主要致病原因，据估计，2008年新增癌症病例1270万例。如果最近主要癌症的趋势继续下去，到2030年，癌症的负担将增加到每年2220万新病例。癌症也是全球主要的死亡原因，2008年有760万人死亡(约占所有死亡人数的13%)。目前市场上出售的磁性氧化铁纳米粒子的饱和磁化强度较低，因此需要高浓度和高外加磁场才能实现有效加热。这一提议旨在制造出比目前使用的磁性纳米颗粒(MNPs)具有更高磁矩的纳米颗粒，并具有更好的性能。建议的过渡元素MNPs是非常可取的，但众所周知，通过精确控制尺寸和尺寸分布来合成它们是出了名的困难。此外，由于它们的磁性(磁矩)显著降低或完全丧失，它们容易被氧化，从而产生有害的影响。用二氧化硅和金等惰性材料包覆纯金属和合金MNPs是保护核心MNPs免受氧化的明显途径。事实证明，由于包覆不完整，这一点具有挑战性，并导致纳米颗粒的长期化学不稳定。此外，目前大多数MNP的合成都是批量进行的，重复性较差。在这个项目中，我们将使用一种新的方法来“桥”包覆MNPs。我们将进一步采用连续流动技术，这是一种能够更好地控制MNPs合成的工具。它允许精确控制操作条件，以及成核、生长和涂覆步骤的空间分离。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，通过设计新颖的合成路线和利用连续流动加工提供的增强功能，推动材料设计和发现的前沿。我们将通过测试MNPs在体外杀死癌细胞的效率，展示我们的合成方法在磁热疗方面的成功，这是抗癌最受欢迎的临床应用之一。

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.