A new nano particulate vehicle for ultrasound enhanced delivery of Cisplatin

一种用于超声增强顺铂输送的新型纳米颗粒载体

• 批准号: EP/L026287/1
• 负责人: Jonathan Knowles
• 金额: $ 86.18万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FL026287%2F1
• 关键词: new; nano; particulate; vehicle; ultrasound

Chemotherapy for the treatment of cancer continues to make great advances. However the current methods of drug delivery rely on injection into a blood vessel and remain very poorly optimised if at all. This results in having to administer high levels of the drug to the whole body, to give local concentrations in the tumour that are effective in reducing or eliminating the tumour. What this means for the patient is significant side effects such as general debilitation, but also the compounds used can be toxic to the kidneys, liver and nerve tissues. One such compound used is called Cisplatin and is the drug of choice for the treatment of head and neck cancers, which have an unacceptably high mortality rate of over 50%. This high mortality rate is due to a number of factors but one of the main factors is that these particular tumour types are quite aggressive and difficult to treat. Thus to develop a delivery system that gives much higher drug concentrations where it is needed would have significant benefits for both the patient and the healthcare provider. One method to deliver drugs to tumours is to utilise nanoparticles. The reason this potentially can be effective is that blood vessels in tumours are "leaky" and will allow nanoparticles to cross from the blood vessel into the tumour. However even though the nanoparticles cross the blood vessel, the particles can show quite poor uptake by the cancer cells. Thus our system aims to combine a nanoparticle within a microbubble. The idea behind the delivery system is that the nanoparticle trapped within the microbubble are injected and an ultrasound probe is applied to the site of the tumour. As the particles passes beneath the ultrasound probe, the ultrasound bursts the bubble and this produces a small shock wave and this has the effect of forcing the nanoparticle across the blood vessel wall and forcing the particle into the cells of the surrounding tumour. This ultimately will give much more localised delivery of the compound meaning enhanced efficacy and reduced side effects for the patient.

治疗癌症的化疗继续取得很大进展。然而，目前的给药方法依赖于血管内注射，即使有优化，也仍然非常糟糕。这导致必须将高水平的药物应用于全身，在肿瘤中给予局部浓度，以有效地减少或消除肿瘤。这对患者意味着显著的副作用，如全身虚弱，但使用的化合物也可能对肾脏、肝脏和神经组织有毒。一种这样的化合物被称为顺铂，是治疗头颈部癌症的首选药物，这类癌症的死亡率高达50%以上，令人无法接受。这种高死亡率是由许多因素造成的，但其中一个主要因素是这些特殊的肿瘤类型具有相当的侵袭性和难以治疗。因此，开发一种给药系统，在需要的地方提供更高的药物浓度，将对患者和医疗保健提供者都有重大好处。将药物输送到肿瘤的一种方法是使用纳米颗粒。这种方法可能有效的原因是，肿瘤中的血管是“漏水的”，并将允许纳米颗粒从血管进入肿瘤。然而，即使纳米颗粒穿过血管，这些颗粒也可能被癌细胞摄取得相当差。因此，我们的系统旨在将纳米颗粒结合到微泡中。传递系统背后的想法是，将捕获在微泡中的纳米颗粒注入，并将超声波探头应用于肿瘤部位。当颗粒通过超声波探头下方时，超声波会使气泡破裂，从而产生一种小冲击波，其效果是迫使纳米颗粒穿过血管壁，迫使颗粒进入周围肿瘤的细胞。这最终将为患者提供更多的局部给药，这意味着增强了疗效，减少了副作用。

项目成果

Organosilica Nanoparticles with an Intrinsic Secondary Amine: An Efficient and Reusable Adsorbent for Dyes.

• DOI: 10.1021/acsami.7b04181
• 发表时间: 2017-05-10
• 期刊: ACS applied materials & interfaces
• 影响因子: 9.5
• 作者: Chen F;Zhao E;Kim T;Wang J;Hableel G;Reardon PJT;Ananthakrishna SJ;Wang T;Arconada-Alvarez S;Knowles JC;Jokerst JV
• 通讯作者: Jokerst JV

Enhanced efficacy in drug-resistant cancer cells through synergistic nanoparticle mediated delivery of cisplatin and decitabine.

• DOI: 10.1039/c9na00684b
• 发表时间: 2020-03-17
• 期刊: Nanoscale advances
• 影响因子: 4.7

Performance of novel high throughput multi electrospray systems for forming of polymeric micro/nanoparticles

• DOI: 10.1016/j.matdes.2017.04.029
• 发表时间: 2017-07-15
• 期刊: MATERIALS & DESIGN
• 影响因子: 8.4
• 作者: Parhizkar, M.;Reardon, P. J. T.;Edirisinghe, M.
• 通讯作者: Edirisinghe, M.