Blanco-Formoso M, Galluzzi F, Vacca F, Gianiorio T, Piergentili I, Cook A B, Welzen P L W, van Hest J C M, Di Marco S, Tantussi F, Benfenati F, Colombo E, De Angelis F
Plasmon Nanotechnology, Istituto Italiano di Tecnologia, Genova, Italy.
CINBIO Universidade de Vigo, Vigo, Spain.
Mater Horiz. 2025 Jul 14;12(14):5302-5314. doi: 10.1039/d5mh00082c.
One of the main challenges in medical applications is achieving precise spatial and temporal control over the release of active molecules, such as neurotransmitters. To address this issue, we engineered a nanovalve that can deliver active molecules on demand by activating or deactivating a light-sensitive chemical barrier. This valve is composed of a polymer containing a spiropyran moiety, which can switch from a hydrophobic to a hydrophilic state upon photo-stimulation. Accordingly, the nanovalve either blocks or allows molecular diffusion through a solid-state nanopore array. Here, we demonstrate that the system blocks up to 96% of the translocation of the neurotransmitter glutamate and that the on-demand release of glutamate upon light stimulation reaches 60 μM h, mimicking a physiological synaptic release rate. We proved its cytocompatibility and analyzed its potential for the stimulation of primary neurons and blind retinal explants by patch-clamp experiments. These results represent a milestone for the development of biomimetic neuroprostheses restoring chemical synaptic transmission lost by degeneration or delivering drugs in a light-controlled fashion.
医学应用中的主要挑战之一是如何对诸如神经递质等活性分子的释放实现精确的空间和时间控制。为了解决这个问题，我们设计了一种纳米阀，它可以通过激活或停用光敏化学屏障按需输送活性分子。该阀由含有螺吡喃部分的聚合物组成，在光刺激下，它可以从疏水状态转变为亲水状态。相应地，纳米阀要么阻止分子扩散通过固态纳米孔阵列，要么允许分子扩散通过。在此，我们证明该系统可阻断高达96%的神经递质谷氨酸的转运，并且光刺激下谷氨酸的按需释放速率达到60 μM/h，模拟了生理突触释放速率。我们通过膜片钳实验证明了其细胞相容性，并分析了其对原代神经元和盲视网膜外植体进行刺激的潜力。这些结果代表了仿生神经假体发展的一个里程碑，该假体可恢复因退化而丧失的化学突触传递，或以光控方式递送药物。
