Key result
Targeted biomimetic rapamycin nanoparticles curb abdominal aortic aneurysm expansion more effectively than nonresponsive controls in rats.
Why the study?
Effective drugs to prevent the growth and delay the rupture of abdominal aortic aneurysms in the clinical setting were lacking. This study aimed to develop a nanotherapy capable of targeting aneurysms and releasing drug molecules in response to the inflammatory microenvironment.
Does a targeted, ROS-responsive rapamycin-loaded nanotherapy coated with cRGDfK peptide and macrophage membrane prevent aneurysm expansion in a rat model of abdominal aortic aneurysm compared to a nonresponsive control nanotherapy?
Does a targeted, ROS-responsive rapamycin-loaded nanotherapy coated with cRGDfK peptide and macrophage membrane prevent aneurysm expansion in a rat model of abdominal aortic aneurysm compared to a nonresponsive control nanotherapy?
Preclinical demonstration that a biomimetic, ROS-responsive rapamycin nanotherapy can selectively target the inflammatory microenvironment of abdominal aortic aneurysms and inhibit aneurysm expansion in rats.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for targeted nanotherapy in aneurysm models; leaves open clinical translation and safety in humans.
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.
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Cheng et al. (2018) studied Abdominal aortic aneurysm (AAA). Rapamycin-loaded reactive oxygen species (ROS)-responsive nanotherapy decorated with peptide ligand cRGDfK and macrophage cell membrane (mean diameter 190 nm) vs. Nonresponsive control nanotherapy was evaluated on Aneurysm expansion in AAA rats and cellular calcification, oxidative stress, and apoptosis in vitro. Intravenously injected 190-nm ROS-responsive rapamycin nanotherapy decorated with cRGDfK and macrophage membrane more effectively prevented aneurysm expansion in AAA rats than nonresponsive control.
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