Engineered Near-infrared Light Sensitive Nanovesicles for Precise Image-Guided Thermally Triggered Cancer Therapy

用于精确图像引导热触发癌症治疗的工程近红外光敏感纳米囊泡

• 批准号: 1790148
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1790148
• 关键词: Engineered; Near; infrared; Light; Sensitive

Nanocarriers have demonstrated great potential to control collateral damage and improve biodistribution of a variety of chemotherapeutic agents. A phenomenon that is key to enable this performance improvement is the preferential accumulation of nanocarriers into a cancerous tissue due the hyperpermeability of its vasculature. However, the heterogeneous tumour distribution and drug release from nanocarriers is an issue.Our aim is to solve the problem engineering multifunctional nanocarriers to combine real-time imaging and triggered release is highly required to achieve precise and efficient therapy. Temperature-responsive vesicles has been attracting increasing attention lately and these vesicular systems have found their way into the clinic (with Thermodox being the most advanced form). However, the heating technologies used to trigger drug release are all based on bulk heating of the tumour mass which has the limitation of uneven and sub-thermal heating.Therefore, to overcome the shortcomings listed above, we propose the engineering of all-in-one image-guided and thermal responsive nano-vesicles that encapsulate anti-cancer drugs in their interior and labelled with light sensitive-clinically approved-indocyanine green (ICG) dye. The ICG near-infrared (NIR) absorbance is essential to allow deep tumour penetration and minimise light scattering. We have shown previously that external activation of ICG-labelled non-temperature sensitive vesicles allows non-invasive dynamic imaging of the distribution into the tumour.In this project we hypothesize that the incorporation of ICG in the outer membrane of thermally triggered vesicles will not only allow the tracking the non-invasive distribution in the tumour mass, but also to transduce the absorbed light radiation by the dye molecules into local heat. The generation of photothermal heating at the nanoscale level in the outer membrane of temperature-sensitive vesicles is expected to be associated with more efficient thermally triggered drug release with less unwanted thermal damage.

纳米载体表现出很大的潜力来控制附带损害并改善各种化学治疗剂的生物分布。这是实现这种绩效的关键的现象是由于其脉管系统的过度过敏性，纳米载体的优先积累到癌组织中。然而，从纳米载体中的异质肿瘤分布和药物释放是一个问题。我们的目的是解决问题工程多功能纳米载体，以结合实时成像和触发释放以实现精确和有效的治疗。温度响应的囊泡最近吸引了越来越多的注意力，这些囊泡系统已经进入了诊所（热门毒素是最先进的形式）。但是，用于触发药物释放的加热技术都是基于对肿瘤质量的大量加热，该肿瘤质量具有不均匀和亚热加热的局限性。因此，要克服上面列出的缺点，我们提出了与抗甲壳的抗癌药物的全合一图像指导和热反应式的纳米式药物的工程工程批准的氨基氨基绿色（ICG）染料。 ICG近红外（NIR）吸光度对于允许深肿瘤穿透并最大程度地减少光散射至关重要。 We have shown previously that external activation of ICG-labelled non-temperature sensitive vesicles allows non-invasive dynamic imaging of the distribution into the tumour.In this project we hypothesize that the incorporation of ICG in the outer membrane of thermally triggered vesicles will not only allow the tracking the non-invasive distribution in the tumour mass, but also to transduce the absorbed light radiation by the dye molecules into local heat.预计温度敏感的囊泡外膜在纳米级水平上的光热加热有望与更有效的热触发药物释放相关，并且不需要的热损伤较少。