Journal
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 72, Issue 21, Pages 2591-2605Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2018.08.2188
Keywords
aneurysm; inflammation; nanotherapy; reactive oxygen species; targeting
Categories
Funding
- National Natural Science Foundation of China [81471774, 81701832]
- Innovation Program for Key Technologies of Southwest Hospital [SWH2016ZDCX1016]
- Science and Technology Innovation Program in Military Medicine of Southwest Hospital [SWH2016LHYS-05]
Ask authors/readers for more resources
BACKGROUND Abdominal aortic aneurysm (AAA) is a leading cause of mortality and morbidity in the elderly. Currently, there remain no effective drugs that can prevent the growth of aneurysms and delay aneurysm rupture in the clinical setting. OBJECTIVES The aim of this study was to develop a nanotherapy that can target aneurysms and release drug molecules in response to the inflammatory microenvironment. METHODS Using a reactive oxygen species (ROS)-responsive nanoparticle and a candidate drug rapamycin, in combination with a peptide ligand for integrin and biomimetic cloaking with macrophage cell membrane, a nanotherapy was developed. Its effectiveness was demonstrated by in vitro and in vivo studies. RESULTS Based on a facile and translational method, a rapamycin-loaded responsive nanotherapy was successfully prepared, which could release drug molecules upon triggering by the high level of ROS. In cells associated with the development of AAAs, the nanotherapy significantly inhibited calcification and attenuated ROS-mediated oxidative stress and apoptosis. By passively targeting aneurysms and releasing drug molecules in response to the inflammatory microenvironment, the intravenously injected ROS-responsive nanotherapy more effectively prevented aneurysm expansion in AAA rats than a nonresponsive control nanotherapy. After decoration with a peptide ligand cRGDfK and macrophage cell membrane, the aneurysmal targeting capability and therapeutic effects of a ROS-responsive nanotherapy with a mean diameter of 190 nm were further enhanced. Moreover, the nanotherapy showed a good safety profile in a preliminary safety test. CONCLUSIONS The multifunctional nanotherapy can be further studied as a promising targeted drug for treatment of aneurysms. The underlying design principles enable the development of a broad range of nanomedicines for targeted therapy of other vascular diseases. (c) 2018 by the American College of Cardiology Foundation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available