Development of Theranostic Nanoparticles; MRI-responsive, thermosensitive drug carriers activated by MRg FUS for local tumour drug release

我们提出的研究计划是关于如何调动物理科学和工程创新的纳米药物载体设计从基础科学实验室到医疗应用。为了做到这一点，米勒教授的化学小组在纳米颗粒技术方面拥有专业知识的Imperial公司将与Maya Thanou博士的制药科学团队（Kings）密切合作，设计、配制和表征MRI响应性热敏药物载体纳米颗粒。（治疗诊断ABC纳米颗粒），具有在癌性病变中积累的能力（纤维瘤或肿瘤），在体内给药后的真实的时间（如通过MRI观察的）。此后，我们将与Gedroyc教授和斯泰宾博士（帝国医学）的研究团队合作，并利用他们的专业知识，证明这些纳米颗粒可以通过磁共振引导聚焦超声（MRgFUS）激活，在相关病变内的纳米颗粒积聚部位局部释放药物。这种组合过程应该能够提供强大的抗癌作用，也可以从根本上改善局部药物生物利用度（仅对肿瘤特异性）和药物疗效，同时最大限度地减少全身药物毒性。纳米颗粒建模和流体动力学研究将由徐教授（帝国，化学工程）的团队进行，以提高我们对递送屏障和药物释放和吸收过程的理解。此后，我们将寻求利用这种理解来优化由我们的医疗保健合作伙伴Antisoma提供的MRgFUS激活的治疗诊断纳米颗粒介导的活性物质体内药物递送。我们预计，Antisoma和我们的其他医疗保健合作伙伴[聚焦超声外科（FUS）基金会和MacMillan Nurses]将在此后的商业化过程中协助我们，包括提供一些用于局部递送的新型抗癌化合物，以提高疗效并降低毒性。

Our proposed research program is concerned with how to mobilize physical science and engineering innovation in nanoparticle drug carrier design from basic science laboratory to medical application. In order to do this, Prof Miller's chemistry team (Imperial) with expertise in nanoparticle technologies, will collaborate closely with Dr Maya Thanou's pharmaceutical sciences team (Kings) in the design, formulation and characterization of MRI-responsive thermosensitive drug carrier nanoparticles (theranostic ABC nanoparticles) that have the capacity to accumulate in cancerous lesions (fibroids or tumours), in real time post administration in vivo (as observed by MRI). Thereafter, we will collaborate with and make use of the expertise of the research teams of Prof Gedroyc and Dr Stebbing (Imperial, Medicine) to demonstrate that these nanoparticles can then be activated by means of magnetic resonance guided focused ultrasound (MRgFUS) to release drug locally at sites of nanoparticle accumulation within the relevant lesion. This combined process should be able to deliver a powerful anti-cancer effect that also improves radically on local drug bioavailability (specific only to tumours) and drug efficacy while minimizing systemic drug toxicity. Nanoparticle modelling and fluid dynamics studies will then be performed by the team of Prof Xu (Imperial, Chemical Engineering) in order to improve our understanding of the delivery barrier and drug release and uptake process. Thereafter we shall seek to take this understanding to optimize MRgFUS-activated theranostic nanoparticle mediated drug delivery of actives in vivo provided by our healthcare partner Antisoma. We anticipate that Antisoma and our other healthcare partners [the Focused Ultrasound Surgery (FUS) Foundation and MacMillan Nurses] will assist us with the commercialization process thereafter including providing some of their novel anti-cancer compounds for local delivery, to increase efficacy and decrease toxicity.