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

治疗诊断纳米颗粒的开发；

• 批准号: EP/I001700/1
• 负责人: Wladyslaw Gedroyc
• 金额: $ 160.18万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FI001700%2F1
• 关键词: Development; Theranostic; Nanoparticles; MRI; responsive

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.

我们提出的研究项目是关于如何调动纳米粒子药物载体设计的物理科学和工程创新从基础科学实验室到医学应用。为了做到这一点，拥有纳米颗粒技术专业知识的Miller教授的化学团队（帝国理工学院）将与Maya Thanou博士的制药科学团队（国王学院）密切合作，设计、配方和表征MRI反应性热敏药物载体纳米颗粒（治疗性ABC纳米颗粒），这些纳米颗粒具有在癌症病变（肌瘤或肿瘤）中积累的能力，在体内实时给药后（通过MRI观察）。之后，我们将与Gedroyc教授和Stebbing博士（帝国医学院）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，在相关病变内纳米颗粒积聚的部位局部释放药物。这种联合过程应该能够提供强大的抗癌效果，同时从根本上提高局部药物生物利用度（仅针对肿瘤）和药物功效，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（帝国理工学院化学工程）的团队进行，以提高我们对输送屏障和药物释放和摄取过程的理解。此后，我们将寻求利用这一认识来优化mrgfus激活的治疗性纳米颗粒介导的体内活性药物递送，该药物递送由我们的医疗保健合作伙伴Antisoma提供。我们期待Antisoma和我们的其他医疗合作伙伴（聚焦超声手术基金会和麦克米伦护士）将在此后的商业化过程中协助我们，包括提供一些新的抗癌化合物用于局部输送，以提高疗效和降低毒性。

项目成果

Towards an integrated systems-based modelling framework for drug transport and its effect on tumour cells.

• DOI: 10.1186/1754-1611-8-3
• 发表时间: 2014
• 期刊: Journal of biological engineering
• 影响因子: 5.6
• 作者: Liu C;Krishnan;Xu XY
• 通讯作者: Xu XY

MR-labelled liposomes and focused ultrasound for spatiotemporally controlled drug release in triple negative breast cancers in mice.

• DOI: 10.7150/ntno.52168
• 发表时间: 2021
• 期刊: Nanotheranostics
• 作者: Amrahli M;Centelles M;Cressey P;Prusevicius M;Gedroyc W;Xu XY;So PW;Wright M;Thanou M
• 通讯作者: Thanou M

Computational modelling of temperature-sensitive liposomal doxorubicin delivery mediated by high intensity focused ultrasound.

高强度聚焦超声介导的温度敏感脂质体阿霉素递送的计算模型。

• 期刊: Pathways into Cancer II,
• 作者: Cong Liu:

Assessment of Hemodynamic Conditions in the Aorta Following Root Replacement with Composite Valve-Conduit Graft

• DOI: 10.1007/s10439-015-1453-x
• 发表时间: 2016-05-01
• 期刊: ANNALS OF BIOMEDICAL ENGINEERING
• 影响因子: 3.8
• 作者: Cheng, Zhuo;Kidher, Emaddin;Xu, Xiao Yun
• 通讯作者: Xu, Xiao Yun

An integrated systems-based modelling framework for investigating the effect of anticancer drugs on solid tumors

用于研究抗癌药物对实体瘤影响的基于系统的集成建模框架

• 发表时间: 2012
• 期刊: American Institute of Chemical Engineers Annual Meeting, Pittsburgh, US,
• 作者: Cong Liu