Department of Radiology, The Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, Guangdong, China.
Department of Neurology, Chengwu County People's Hospital, Chengwu 274200, Shandong, China.
ACS Appl Mater Interfaces. 2021 Dec 8;13(48):56909-56922. doi: 10.1021/acsami.1c16530. Epub 2021 Nov 22.
Stroke is the second leading cause of death globally and the most common cause of severe disability. Several barriers need to be addressed more effectively to treat stroke, including efficient delivery of therapeutic agents, rapid release at the infarct site, precise imaging of the infarct site, and drug distribution monitoring. The present study aimed to develop a bio-responsive theranostic nanoplatform with signal-amplifying capability to deliver rapamycin (RAPA) to ischemic brain tissues and visually monitor drug distribution. A pH-sensitive theranostic RAPA-loaded nanoparticle system was designed since ischemic tissues have a low-pH microenvironment compared with normal tissues. The nanoparticles demonstrated good stability and biocompatibility and could efficiently load rapamycin, followed by its rapid release in acidic environments, thereby improving therapeutic accuracy. The nano-drug-delivery system also exhibited acid-enhanced magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging signal properties, enabling accurate multimodal imaging with minimal background noise, thus improving drug tracing and diagnostic accuracy. Finally, in vivo experiments confirmed that the nanoparticles preferentially aggregated in the ischemic hemisphere and exerted a neuroprotective effect in rats with transient middle cerebral artery occlusion (tMCAO). These pH-sensitive multifunctional theranostic nanoparticles could serve as a potential nanoplatform for drug tracing as well as the treatment and even diagnosis of acute ischemic stroke. Moreover, they could be a universal solution to achieve accurate in vivo imaging and treatment of other diseases.
中风是全球第二大致死原因，也是导致严重残疾的最常见原因。为了治疗中风，需要更有效地解决几个障碍，包括治疗剂的有效输送、在梗塞部位的快速释放、梗塞部位的精确成像以及药物分布监测。本研究旨在开发一种具有信号放大能力的生物响应治疗纳米平台，将雷帕霉素（RAPA）递送至缺血性脑组织，并进行可视化药物分布监测。由于与正常组织相比，缺血组织具有低 pH 的微环境，因此设计了一种 pH 敏感的治疗性载雷帕霉素纳米粒子系统。这些纳米粒子表现出良好的稳定性和生物相容性，能够有效地负载雷帕霉素，随后在酸性环境中快速释放，从而提高治疗的准确性。该纳米药物递送系统还表现出酸增强磁共振成像（MRI）和近红外荧光（NIRF）成像信号特性，能够进行准确的多模态成像，具有最小的背景噪声，从而提高药物追踪和诊断的准确性。最后，体内实验证实，纳米粒子优先聚集在缺血半球，并在短暂性大脑中动脉闭塞（tMCAO）大鼠中发挥神经保护作用。这些 pH 敏感的多功能治疗性纳米粒子可作为一种潜在的纳米平台，用于药物追踪以及治疗甚至诊断急性缺血性中风。此外，它们可能是实现其他疾病的精确体内成像和治疗的通用解决方案。
