pH-Responsive Multifunctional Theranostic Rapamycin-Loaded Nanoparticles for Imaging and Treatment of Acute Ischemic Stroke
pH-Responsive Multifunctional Theranostic Rapamycin-Loaded Nanoparticles for Imaging and Treatment of Acute Ischemic Stroke
复制标题
pH 响应型多功能治疗诊断载雷帕霉素纳米颗粒用于急性缺血性中风的成像和治疗
DOI：
10.1021/acsami.1c16530
复制
发表时间：
2021-12-08
影响因子：
9.5
通讯作者：
Wu, Renhua
中科院分区：
文献类型：
--
作者：
Cheng, Yan;Cheng, Airong;Wu, Renhua
中风是全球第二大死亡原因，也是导致严重残疾的最常见原因。为了更有效地治疗中风，需要更有效地解决几个障碍，包括治疗药物的有效输送、梗死部位的快速释放、梗死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性治疗纳米平台，将雷帕霉素(RapA)输送到缺血脑组织，并可直观地监测药物分布。针对缺血组织与正常组织相比具有低pH微环境的特点，设计了一种pH敏感的RAPA纳米微粒系统。纳米粒表现出良好的稳定性和生物相容性，可以有效地负载雷帕霉素，然后在酸性环境中快速释放，从而提高治疗的准确性。纳米药物输送系统还显示出酸增强磁共振成像(MRI)和近红外荧光(NIRF)成像信号特性，能够以最小的背景噪声进行准确的多模式成像，从而提高药物示踪和诊断的准确性。最后，体内实验证实，纳米粒优先聚集在缺血侧大脑半球，对短暂性大脑中动脉闭塞(TMCAO)大鼠具有神经保护作用。这些对pH敏感的多功能纳米微粒可以作为潜在的纳米平台用于药物示踪以及急性缺血性卒中的治疗甚至诊断。此外，它们可以成为一种通用的解决方案，以实现对其他疾病的准确体内成像和治疗。
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 nano-particle 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.