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

纳米载体在控制附带损伤和改善多种化疗药物的生物分布方面表现出巨大的潜力。能够实现这种性能改善的关键现象是纳米载体由于其脉管系统的高渗透性而优先积累到癌组织中。然而，肿瘤的不均匀分布和纳米载体的药物释放是一个问题，我们的目标是解决这个问题，工程多功能纳米载体结合联合收割机实时成像和触发释放是非常需要的，以实现精确和有效的治疗。温度响应性囊泡最近引起了越来越多的关注，这些囊泡系统已经进入临床（Thermodox是最先进的形式）。然而，用于触发药物释放的加热技术都是基于对肿瘤块体的整体加热，其具有不均匀和亚热加热的局限性。因此，为了克服上述缺点，我们提出了一体化图像引导和热响应纳米囊泡的工程设计，该囊泡在其内部封装抗癌药物，并标记有光敏临床批准的吲哚菁绿色（ICG）染料。ICG近红外（NIR）吸收对于允许深度肿瘤穿透和最小化光散射至关重要。我们已经表明，ICG标记的非温度敏感囊泡的外部激活允许非侵入性的动态成像的分布到tumor.In这个项目中，我们假设，在热触发囊泡的外膜中的ICG的掺入不仅允许跟踪的非侵入性分布在肿瘤块，但也将吸收的光辐射的染料分子转化为局部热。在温度敏感囊泡的外膜中在纳米级水平上产生光热加热预期与更有效的热触发药物释放相关，具有更少的不必要的热损伤。

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.