Abstract：
In this work, for the first time, we demonstrate light control of a therapeutic protein\'s release from a depot in the subcutaneous layer of the skin. The subcutaneous layer is a standard location for therapeutic protein depots due to its large size and ease of access, but prior attempts to utilize this space failed because insufficient light can reach this deeper layer. An analysis of existing biophysical literature suggested that an increase of photoactivation wavelength from 365 to 500 nm could allow an increase of depot irradiation in the subcutaneous by >100-fold. We therefore used a green light-activated thio-coumarin-based material and demonstrated robust release of a therapeutic, insulin, in response to skin illumination with an LED light source. We further demonstrated that this release is ultrafast, as fast or faster than any commercially used insulin, while maintaining the native insulin sequence. This release of insulin was then accompanied by a robust reduction in blood glucose, demonstrating the retention of bioactivity despite the synthetic processing required to generate the material. In addition, we observed that the material exhibits slow basal release of insulin, even in the absence of light, potentially through biochemical or photochemical unmasking of insulin. Thus, these materials can act much like the healthy pancreas does: releasing insulin at a slow basal rate and then, upon skin irradiation, releasing an ultrafast bolus of native insulin to reduce postprandial blood glucose excursions.
摘要：
在这项工作中,第一次,我们证明了治疗性蛋白质从皮下储库中释放的光控制。由于其大尺寸和易于进入，皮下层是治疗性蛋白质库的标准位置，但是先前利用这个空间的尝试失败了，因为没有足够的光可以到达这个更深的层。对现有生物物理文献的分析表明，光活化波长从365nm增加到500nm可以使皮下储库辐射增加>100倍。因此，我们使用了绿色光活化的硫代香豆素基材料，并证明了一种治疗剂的强劲释放，胰岛素，响应于具有LED光源的皮肤照明。我们进一步证明了这个版本是超快的，与任何商业使用的胰岛素一样快或更快，同时保持天然胰岛素序列。然后，胰岛素的释放伴随着血糖的强劲降低，证明了生物活性的保留，尽管合成加工需要产生的材料。此外,我们观察到该材料表现出胰岛素的缓慢基础释放，即使在没有光的情况下，可能通过生化或光化学揭开胰岛素的面纱。因此，这些物质可以像健康的胰腺一样发挥作用：以缓慢的基础速率释放胰岛素，然后，在皮肤照射后，释放天然胰岛素的超快丸剂以减少餐后血糖波动。
