pH-Responsive Multifunctional Theranostic Rapamycin-Loaded Nanoparticles for Imaging and Treatment of Acute Ischemic Stroke.

Abstract

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.

• Authors: Yan Cheng, Airong Cheng, Yanlong Jia, Lin Yang, Yan Ning, Liang Xu, Yazhi Zhong, Zerui Zhuang, Jitian Guan, Xiaolei Zhang, Yan Lin, Teng Zhou, Xiusong Fan, Jianwu Li, Peng Liu, Gen Yan, Renhua Wu
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 13 Issue 48 Pg. 56909-56922 (Dec 08 2021) ISSN: 1944-8252 [Electronic] United States
• PMID: 34807583 (Publication Type: Journal Article)

Chemical References

• Neuroprotective Agents
• Sirolimus

Topics

• Acute Disease
• Animals
• Biomimetic Materials (chemistry, therapeutic use)
• Hydrogen-Ion Concentration
• Ischemic Stroke (diagnostic imaging, drug therapy)
• Materials Testing
• Nanoparticles (chemistry)
• Neuroprotective Agents (chemistry, therapeutic use)
• PC12 Cells
• Particle Size
• Rats
• Sirolimus (chemistry, therapeutic use)
• Theranostic Nanomedicine