Magnetic delivery of anit-cancer magnetosomes using MRI

背景：随着FDA最近批准安进的T-VEC（一种溶瘤病毒）治疗黑色素瘤，用于摧毁癌症的溶瘤病毒疗法已迅速被接受为癌症治疗方式。然而，静脉给药后溶瘤病毒（OV）被宿主防御机制大量破坏，限制了对可接近的肿瘤的适用性，在这些肿瘤中直接注射OV是必要的。核磁共振成像扫描仪提供了新的机会，以磁力引导抗癌治疗准确地针对肿瘤。我们假设，使用MRT精确递送OVs将大大提高注射到血液中的治疗效果，同时防止不必要的病毒免疫攻击。该项目的目的是：(1)利用核磁共振扫描仪的强脉冲磁场梯度将磁小体- ov复合物（mago - ov）传递给转移性肿瘤小鼠。核磁共振扫描仪还将用于通过生成治疗组织的纵向图像来跟踪给药后的治疗(2)使用数学模型来(i)确定靶向方案中的关键物理过程，（ii）预测MRT在其他小鼠癌症模型中的功效（iii）将其扩展到人类应用。

Background: Oncolytic virotherapy to destroy cancer has fast gained acceptance as acancer treatment modality with the recent FDA approval for Amgen's T-VEC (an oncolyticHSV) in melanoma. However, following intravenous administration oncolytic viruses (OV) aremassively compromised by host defense mechanisms limiting applicability to accessibletumours where injection of OV directly into the tumour is necessary. MRI scanners offer newopportunities to magnetically guide anticancer therapies accurately to tumours. Wehypothesise that such precise delivery of OVs using MRT will massively improve therapeuticefficacy following injection into the blood stream, whilst preventing unwanted immune attackof the virus.The Aims of this project are (1) To use the powerful-pulsed magnetic field gradient of an MRIscanner to deliver magnetosome-OV complexes (Mag-OV) to mice with metastatic tumours.The MRI scanner will also be used also be used to track therapy after administration bygenerating longitudinal images of the treated tissue (2) To use mathematical models to (i)identify the key physical processes in the targeting protocol, (ii) predict efficacy of MRT inother murine cancer models (iii) to scale it up to application in humans.