颞叶癫痫是由大脑异常同步化放电引起的神经系统常见病。目前临床上主要是通过长期服用抗癫痫药物来控制癫痫发作，但是药物治疗存在靶向性差和毒副作用大等问题。提高脑内癫痫灶的药物浓度以快速阻断癫痫电信号的传播是抑制癫痫发作并降低毒副作用的关键。申请人及所在课题组前期在聚吡咯材料中引入聚多巴胺制备了电响应型抗癫痫纳米载药系统，并通过主动靶向多肽修饰实现药物的脑靶向递送。预实验结果表明该系统可以实现药物长效负载和电场响应释放，并初步发现其具有较好的抗癫痫疗效。本项目拟进一步利用多肽介导和光控诱导的联合靶向技术，明确材料功能化与靶向效率的关系；研究药物释放动力学，阐明电场响应释放药物的作用特征；利用不同急慢性癫痫模型，明确载药系统的抗癫痫作用机制及生物安全性。本项目围绕癫痫发作的电生理学机制，运用联合靶向技术和材料电响应特性，通过多学科交叉研究纳米载药系统的抗癫痫作用，将为癫痫药物治疗提供新方案。

Temporal lobe epilepsy is a common neurological disease caused by abnormal synchronized discharge in the brain and it is mainly treated through long-term use of anti-epileptic drugs (AEDs). However, there are many problems that exist with current AEDs treatments such as non-specific drug targeting, toxicity, and other adverse effects. To address these issues, we can increase the local concentration of AEDs in the dysfunctional area of the brain in order to promptly block the transmission of epileptic electrical signals. This strategy is considered as a powerful tool to suppress epileptic seizure and reduce the side effects. Herein, we introduce an electro-responsive targeting drug delivery system (DDS) on the basis of polydopamine and polypyrrole that targets dysfunctional regions of the brain. The preliminary data indicates that this DDS is capable of efficient drug loading and electro-responsive release of AEDs while at the same time exhibiting satisfactory anti-epileptic efficacy. Therefore, this project is supposed to 1) clarify the relationship between the multifunctional modality and the targeting efficiency of DDS by using a peptide-mediated and near-infrared light-induced dual-targeting strategy, 2) investigate the drug release kinetics and the characteristics of electro-responsive release, 3) illustrate the anti-epileptic mechanism and biosafety profiles of the DDS by using classic models of acute and chronic epilepsy. In summary, this interdisciplinary research will focus on the electrophysiological mechanism of epileptic seizures and make full use of the combined targeting strategy and the electro-responsive property of the DDS, which holds great promises for enhanced epilepsy therapy.