New Imaging Methods for Functional Changes in Diagnostic Nanocomposite Particles

诊断纳米复合颗粒功能变化的新成像方法

• 批准号: BB/X003957/1
• 负责人: Marco Giardiello
• 金额: $ 22.96万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX003957%2F1
• 关键词: New; Imaging; Methods; Functional; Changes

Background: Inorganic/Organic Nanocomposite Particles (I/O-NP) are being developed for use in diagnostic medicine. I/O-NP is a platform technology that is composed of functional polymeric organic nanoscale structures (50-200 nm) in which smaller metallic nanoparticles (2-20 nm) are encapsulated. I/O-NPs offer a new class of biologically responsive, functional materials through fine tuning nanostructure composition and architecture. The encapsulation of magnetic iron oxide nanoparticles within biologically responsive organic nanostructures are being developed; polymeric particles are designed to swell or contract in response to biological stimuli, causing reversible variation of interparticle proximity and rotation dynamics of the encapsulated iron oxide nanoparticles, which would elicit a responsive behaviour in their magnetic signal. Such stimuli could be achieved through tailored I/O-NP synthesis to incorporate disease specific targeting vectors or antibodies, allowing for disease pathogen and viral load quantification in response to pharmaceutical intervention. On an individual patient basis, such quantitative disease state monitoring would accelerate the transition from conventional medicine towards personalised, precision medicine. In the long-term, acquired data from larger patient cohort monitoring following response to drug dosage would be integrated into in-silico models to allow for greater predictive power for medical prescription, allowing for population driven predictive modelling towards optimising global drug regimen administration.Problem: The detection of discrete, key functional changes in I/O-NP structure following biological stimulation. I/O-NPs offer novel functionality beyond traditional diagnostic imaging tracers. However, current standard detection methods are not capable of monitoring their key functional changes; imaging techniques such as MRI as well as laboratory techniques such as SQUID are not sensitive enough to detect such fine variation of magnetic signal.Solution: To develop a prototype scanner, termed FS-MPI. The proposed novel device combines the principles of frequency dependent detection of magnetic susceptibility (FS) with the ultrasensitive detection mechanism of Magnetic Particle Imaging (MPI). MPI is a highly sensitive, emerging imaging technique able to detect nanomolar concentrations of Superparamagnetic Iron Oxide Nanoparticle (SPION) tracers. Magnetic tracers are imaged directly allowing for highly sensitive, quantitative detection with no background signal. Furthermore, MPI allows for both quantification and real-time functional imaging with more than a thousand-fold contrast-to-noise improvement on a per-mole basis over MRI, providing bright contrast. Through the combination of MPI with techniques established for characterising ferromagnetic and superparamagnetic thin film nanostructures (e.g. AC susceptibility; the background of the Solution Provider), a new FS-MPI imaging modality is proposed which offers the prospect of detecting such changes. MPI technologies are driven by tracer development and thus represents enormous potential for novelty and innovation through Advanced Materials Research if coupled with new imaging modalities for probing such functional tracers. Development of a prototype FS-MPI system designed to measure the functional behaviour of I/O-NP is highly ambitious, and the combination of novel I/O-NP material development and prototype imaging device for detection will create enormous potential for innovation for new diagnostic technologies, both in vivo and in vitro.

背景：正在开发用于诊断医学的无机/有机纳米复合颗粒（I/O-NP）。 I/O-NP是一种平台技术，由功能性聚合物有机纳米级结构（50-200 nm）组成，其中封装了较小的金属纳米颗粒（2-20 nm）。 I/O-NP通过微调纳米结构组成和体系结构提供了新的生物学响应式功能材料。正在开发在生物响应的有机纳米结构中磁氧化铁纳米颗粒的封装；聚合物颗粒被设计为响应生物学刺激的肿胀或收缩，从而导致颗粒间接近性的可逆变化和封装的氧化铁纳米颗粒的旋转动力学，这会在其磁信号中引起响应性行为。可以通过量身定制的I/O-NP合成来实现此类刺激，以结合疾病特定的靶向载体或抗体，从而允许疾病的病原体和病毒负荷定量响应药物干预。在个人患者的基础上，这种定量疾病状态监测将加速从常规医学向个性化的精密医学过渡。从长远来看，对药物剂量的反应后，从较大的患者队列监测中获得的获得的数据将集成到硅内模型中，以使医疗处方的预测能力具有更大的预测能力，从而允许人口驱动的预测性建模，以优化全球药物治疗剂。 I/O-NP提供了传统诊断成像示踪剂以外的新功能。但是，当前的标准检测方法无法监视其关键功能变化。成像技术（例如MRI）以及实验室技术（例如鱿鱼）不足以检测到磁信号的良好变化。解决：开发原型扫描仪，称为FS-MPI。提出的新型设备将磁化率（FS）的频率依赖性检测原理与磁性粒子成像（MPI）的超敏感检测机理（MPI）结合在一起。 MPI是一种高度敏感的，新兴的成像技术，能够检测纳摩尔浓度的超顺磁性氧化铁纳米颗粒（SPION）示踪剂。直接对磁性示踪剂进行成像，允许没有背景信号的高度敏感，定量检测。此外，MPI允许进行定量和实时功能成像，并以每级MRI为基础的一千多倍对比度改进，从而提供明亮的对比度。通过将MPI与用于表征铁磁和超磁性薄膜纳米结构（例如AC敏感性；解决方案提供商的背景）的技术组合，提出了一种新的FS-MPI成像方式，该模态提出了一种可检测此类变化的前景。 MPI技术是由示踪剂开发驱动的，因此，如果与新成像方式相结合以探测此类功能示踪剂，则可以通过先进的材料研究来实现新颖性和创新的巨大潜力。旨在衡量I/O-NP功能行为的原型FS-MPI系统的开发是高度雄心勃勃的，并且新型I/O-NP材料开发和用于检测的原型成像设备的结合将为新的诊断技术创新带来巨大的潜力，包括在体内和体外。