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：无机/有机纳米复合颗粒（I/O-NP）正在开发用于诊断医学。 I/O-NP 是一种平台技术，由功能性聚合有机纳米级结构（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结构，提供了一种新型生物响应功能材料。正在开发将磁性氧化铁纳米颗粒封装在生物响应性有机纳米结构中；聚合物颗粒被设计为响应生物刺激而膨胀或收缩，导致封装的氧化铁纳米颗粒的颗粒间接近度和旋转动力学的可逆变化，这将引起其磁信号的响应行为。这种刺激可以通过定制的 I/O-NP 合成来实现，以纳入疾病特异性靶向载体或抗体，从而可以根据药物干预对疾病病原体和病毒载量进行定量。在个体患者的基础上，这种定量的疾病状态监测将加速从传统医学向个性化、精准医学的转变。从长远来看，从对药物剂量反应后的较大患者队列监测中获取的数据将被整合到计算机模型中，以便为医疗处方提供更大的预测能力，从而实现人口驱动的预测模型，以优化全球药物治疗方案的管理。 问题：生物刺激后 I/O-NP 结构中离散的关键功能变化的检测。 I/O-NP 提供超越传统诊断成像示踪剂的新颖功能。然而，目前的标准检测方法无法监测其关键功能变化； MRI 等成像技术以及 SQUID 等实验室技术不够灵敏，无法检测磁信号的如此细微变化。解决方案：开发原型扫描仪，称为 FS-MPI。所提出的新颖装置将磁化率（FS）的频率相关检测原理与磁粒子成像（MPI）的超灵敏检测机制相结合。 MPI 是一种高度灵敏的新兴成像技术，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。磁性示踪剂直接成像，可实现高灵敏度、无背景信号的定量检测。此外，MPI 可以实现量化和实时功能成像，每摩尔的对比度与噪声比 MRI 提高了一千倍以上，提供了明亮的对比度。通过将 MPI 与用于表征铁磁和超顺磁薄膜纳米结构的技术（例如交流磁化率；解决方案提供商的背景）相结合，提出了一种新的 FS-MPI 成像模式，它提供了检测此类变化的前景。 MPI 技术由示踪剂开发驱动，因此如果与探测此类功能示踪剂的新成像模式相结合，通过先进材料研究代表了新颖性和创新的巨大潜力。开发用于测量 I/O-NP 功能行为的原型 FS-MPI 系统是非常雄心勃勃的，新颖的 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创新创造巨大的潜力。体内和体外诊断技术。