Bubble Therapy: a New Paradigm for Targeted Drug Delivery by Ultrasound

气泡疗法：超声靶向给药的新范例

• 批准号: EP/F011547/1
• 负责人: Constantin Coussios
• 金额: $ 140.57万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FF011547%2F1
• 关键词: Bubble; Therapy; New; Paradigm; Targeted

High amplitude ultrasound waves propagating through tissue have been recently reported to induce a range of potentially beneficial phenomena, such as rapid tissue heating, increased permeability of cells to large drug molecules (sonoporation) or enhanced activity of drugs. These bioeffects are heavily correlated with the ultrasound-induced nucleation and subsequent excitation of micron-sized bubbles, yielding two types of acoustic cavitation activity: (1) inertial cavitation, which dramatically increases the energy transfer to tissue and can cause rapid heating and mechanical damage, and (2) stable cavitation, whereby bubbles act as micropumps that dramatically enhance the local mixing and transport length scales of drug molecules. In cancer treatment, local heating combined with chemotherpay will render cancer cells more sensitive to treatment, whilst local micropumping of the drug can help overcome delivery problems arising from the highly complex tumour structure. In the context of breaking down blood clots for stroke therapy, cavitation-enhanced mixing will promote delivery of the drug to a site of low blood flow and greatly increase the diffusion of the thombolyic drug across the clot surface.However, the nucleation of cavitating microbubbles and subsequent interaction with cells in biologically relevant media remain poorly understood. The objectives of the proposed research therefore are (i) to investigate the potential of cell- and site-specific cavitation nucleation using commercially available targeted nanoparticles currently being developed for molecular imaging; (ii) to understand and optimize the mechanism by which ultrasound and cavitation can enhance local drug delivery and drug activity across inaccessible interfaces such as tumours or blood clots; (iii) to develop clinically relevant means of monitoring cavitation activity and exploit them for real-time monitoring of drug delivery and (iv) to test the optimized drug delivery and treatment monitoring protocols in a clinically relevant organ model.It is hoped that the proposed resarch will pave the road for widespread clinical uptake of cavitaiton-enhanced targeted drug delivery by ultrasound. Particular advantages of this technique will include the ability to locally enhance drug activity, thus reducing the necessary drug dosages and their side effects, and to monitor therapy in real time. The outcomes of the proposed research are expected to be directly transferable to many other novel therapeutic ultrasound applications, such as non-invasive tissue ablation by High-Intensity Focussed Ultrasound (HIFU), acoustic haemostasis and ultrasound-induced opening of the blood-brain barrier for transcranial drug delivery.

最近有报道称，在组织中传播的高幅度超声波可以引起一系列潜在的有益现象，例如快速的组织加热、细胞对大分子药物的渗透性增加(声波治疗)或增强药物的活性。这些生物效应与超声诱导微米级气泡的成核和随后的激发密切相关，从而产生两种类型的声空化活动：(1)惯性空化，极大地增加向组织的能量传递，并可导致快速加热和机械损伤；(2)稳定空化，气泡充当微泵，极大地增强药物分子的局部混合和传输长度。在癌症治疗中，局部加热与化疗相结合将使癌细胞对治疗更敏感，而局部微泵药物可帮助克服高度复杂的肿瘤结构引起的输送问题。在中风治疗中，空化增强的混合将促进药物向低血流部位的输送，并极大地增加血栓表面的药物扩散。然而，空化微泡的成核以及随后与生物相关介质中的细胞的相互作用仍然知之甚少。因此，拟议研究的目标是：(I)使用目前正在开发的用于分子成像的商用靶向纳米颗粒，研究特定细胞和部位的空化成核的可能性；(Ii)了解和优化超声和空化可以增强局部药物输送和跨越肿瘤或血栓等难以接触的界面的药物活性的机制；(Iii)开发临床上相关的监测空化活动的手段，并将其用于药物输送的实时监测；(Iv)在临床相关的器官模型中测试优化的药物输送和治疗监测方案。希望拟议的研究将为空泡增强的超声靶向输送在临床上的广泛应用铺平道路。这项技术的特殊优势将包括能够在局部增强药物活性，从而减少必要的药物剂量及其副作用，并实时监测治疗情况。这项研究的成果有望直接应用于其他许多新的治疗性超声应用，如高强度聚焦超声(HIFU)的非侵入性组织消融、声学止血和超声诱导的血脑屏障开放以用于经颅给药。

项目成果

Targeting of liposomes via PSGL1 for enhanced tumor accumulation.

通过 PSGL1 靶向脂质体以增强肿瘤积累。

• DOI: 10.1007/s11095-012-0875-5
• 发表时间: 2013-02
• 期刊: PHARMACEUTICAL RESEARCH
• 影响因子: 3.7
• 作者: Carlisle, Robert;Seymour, Leonard W.;Coussios, Constantin C.
• 通讯作者: Coussios, Constantin C.

Enhanced tumor uptake and penetration of virotherapy using polymer stealthing and focused ultrasound.

• DOI: 10.1093/jnci/djt305
• 发表时间: 2013-11-20
• 期刊: Journal of the National Cancer Institute
• 作者: Carlisle R;Choi J;Bazan-Peregrino M;Laga R;Subr V;Kostka L;Ulbrich K;Coussios CC;Seymour LW
• 通讯作者: Seymour LW

Cavitation-enhanced delivery of a replicating oncolytic adenovirus to tumors using focused ultrasound

• DOI: 10.1016/j.jconrel.2013.03.017
• 发表时间: 2013-07-10
• 期刊: JOURNAL OF CONTROLLED RELEASE
• 影响因子: 10.8
• 作者: Bazan-Peregrino, Miriam;Rifai, Bassel;Coussios, Constantin C.
• 通讯作者: Coussios, Constantin C.

Improving Delivery of Oncolytic Viruses to Solid Tumours

改善溶瘤病毒向实体瘤的递送

• 发表时间: 2014
• 期刊: HUMAN GENE THERAPY
• 影响因子: 4.2
• 作者: Carlisle R.